1 00:00:05,600 --> 00:00:07,800 GOOD AFTERNOON, EVERYONE. 2 00:00:07,800 --> 00:00:09,760 WELCOME TO THE WEDNESDAY 3 00:00:09,760 --> 00:00:12,280 AFTERNOON LECTURE SERIES. 4 00:00:12,280 --> 00:00:15,240 I'M PAM ROBY, CHIEF OF SKELETAL 5 00:00:15,240 --> 00:00:16,760 BIOLOGY SECTION AT THE NATIONAL 6 00:00:16,760 --> 00:00:19,000 INSTITUTE OF DENTAL AND 7 00:00:19,000 --> 00:00:20,360 CRANIOFACIAL RESEARCH. 8 00:00:20,360 --> 00:00:25,560 OUR SPEAKER TODAY, DR. CLIFFORD 9 00:00:25,560 --> 00:00:26,120 TABIN, GEORGE JACOB AND 10 00:00:26,120 --> 00:00:28,280 JACQUELINE HAZEL LEDER PROFESSOR 11 00:00:28,280 --> 00:00:31,840 OF GENETICS AND CHAIR OF THE 12 00:00:31,840 --> 00:00:32,560 DEPARTMENT OF GENETICS, HARVARD 13 00:00:32,560 --> 00:00:34,840 MEDICAL SCHOOL. 14 00:00:34,840 --> 00:00:38,040 DR. TABIN RECEIVED HIS 15 00:00:38,040 --> 00:00:40,320 UNDERGRADUATE DEGREE FROM 16 00:00:40,320 --> 00:00:43,640 UNIVERSITY OF CHICAGO IN 1976, 17 00:00:43,640 --> 00:00:48,040 HIS Ph.D. FROM M.I.T. IN 1984. 18 00:00:48,040 --> 00:00:49,800 HE THEN UNDERTOOK POSTDOCTORAL 19 00:00:49,800 --> 00:00:50,600 FELLOWSHIPS AT HARVARD 20 00:00:50,600 --> 00:00:55,040 UNIVERSITY AND MASSACHUSETTS 21 00:00:55,040 --> 00:00:56,560 GENERAL HOSPITAL BEFORE 22 00:00:56,560 --> 00:00:57,240 SETTLINGS AT HARVARD MEDICAL 23 00:00:57,240 --> 00:01:00,280 SCHOOL, ACCEPTED A POSITION OF 24 00:01:00,280 --> 00:01:01,480 ASSISTANT PROFESSOR THERE IN 25 00:01:01,480 --> 00:01:06,200 1989, BECAME A FULL PROFESSOR IN 26 00:01:06,200 --> 00:01:06,680 1997. 27 00:01:06,680 --> 00:01:10,920 CONCURRENTLY HE BECAME AN 28 00:01:10,920 --> 00:01:14,200 ADJUNCT PROFESSOR AT M.I.T, A 29 00:01:14,200 --> 00:01:15,680 POSITION HE STILL MAINTAINS, 30 00:01:15,680 --> 00:01:18,000 BECAME CHAIRMAN OF THE 31 00:01:18,000 --> 00:01:19,560 DEPARTMENT OF GENETICS AT 32 00:01:19,560 --> 00:01:23,360 HARVARD IN 2007. 33 00:01:23,360 --> 00:01:24,800 DR. TABIN MADE SEMINAL 34 00:01:24,800 --> 00:01:30,760 DISCOVERIES ALONG WITH PHIL 35 00:01:30,760 --> 00:01:35,040 GRAHAM AND ANDREW MAYHEM OF 36 00:01:35,040 --> 00:01:36,600 HEDGE HOG GENES IN VERTEBRATES, 37 00:01:36,600 --> 00:01:43,880 FORM AND FUNCTION IN EMBRYONIC 38 00:01:43,880 --> 00:01:46,680 VERTEBRATE, AND TIME TO GENERATE 39 00:01:46,680 --> 00:01:48,040 STORIED DIVERSITY OF ANIMAL 40 00:01:48,040 --> 00:01:50,320 FORMS ON THIS PLANET. 41 00:01:50,320 --> 00:01:52,920 THEY COMBINED CLASSICAL METHODS 42 00:01:52,920 --> 00:01:56,720 OF EXPERIMENTAL EMBRYOLOGY WITH 43 00:01:56,720 --> 00:01:59,680 MODERN MOLECULAR IMAGING, 44 00:01:59,680 --> 00:02:02,440 GENETIC, GENOMIC TECHNIQUES FOR 45 00:02:02,440 --> 00:02:04,640 INTERROGATING GENE FUNCTION. 46 00:02:04,640 --> 00:02:12,040 IN HIS EVOLUTIONARY WORK 47 00:02:12,040 --> 00:02:14,800 ADDRESSED QUESTIONS OF BEHAVIOR 48 00:02:14,800 --> 00:02:16,440 AND METABOLIC EVOLUTION USING 49 00:02:16,440 --> 00:02:17,720 DEVELOP MEMORIAL AND GENETIC 50 00:02:17,720 --> 00:02:18,040 APPROACHES. 51 00:02:18,040 --> 00:02:20,800 IN TODAY'S TALK HE TURNS TO 52 00:02:20,800 --> 00:02:22,640 BIRDS, AND THEIR REMARKABLE 53 00:02:22,640 --> 00:02:26,920 ABILITY TO VOCALIZE WITH AN 54 00:02:26,920 --> 00:02:29,000 ORGAN CALLED THE SYRINX, 55 00:02:29,000 --> 00:02:30,200 PRODUCING SOUNDS WITHOUT VOCAL 56 00:02:30,200 --> 00:02:31,440 FOLDS MAMMALS HAVE. 57 00:02:31,440 --> 00:02:33,240 DR. TABIN HAS BEEN A MEMBER OF 58 00:02:33,240 --> 00:02:37,840 THE NATIONAL ACADEMY OF SCIENCES 59 00:02:37,840 --> 00:02:39,120 SINCE 2007, ALSO IS ELECTED TO 60 00:02:39,120 --> 00:02:43,120 THE AMERICAN ACADEMY OF ARTS AND 61 00:02:43,120 --> 00:02:45,600 SCIENCES, EUROPEAN MOLECULAR 62 00:02:45,600 --> 00:02:46,680 BIOLOGY ORGANIZATION, ROYAL 63 00:02:46,680 --> 00:02:49,840 SOCIETY OF LONDON AS A FOREIGN 64 00:02:49,840 --> 00:02:50,080 MEMBER. 65 00:02:50,080 --> 00:02:56,600 HE HAS BEEN AWARDED THE EDWIN 66 00:02:56,600 --> 00:02:59,360 CONKLIN MEDAL, MARCH OF DIMES 67 00:02:59,360 --> 00:03:00,640 PRIZE IN DEVELOPMENTAL BIOLOGY 68 00:03:00,640 --> 00:03:04,040 AND HAS WON NUMEROUS AWARDS FOR 69 00:03:04,040 --> 00:03:06,120 HIS TEACHING AT HARVARD MEDICAL 70 00:03:06,120 --> 00:03:07,840 SCHOOL AND IT'S REALLY A 71 00:03:07,840 --> 00:03:10,400 PLEASURE TO HAVE HIM HERE TODAY. 72 00:03:10,400 --> 00:03:13,120 THE TITLE OF THE TALK IS "HOW 73 00:03:13,120 --> 00:03:16,720 DID BIRDS EVOLVE THE CAPACITY TO 74 00:03:16,720 --> 00:03:17,200 VOCALIZE." 75 00:03:17,200 --> 00:03:18,280 DR. TABIN, WELCOME, AND THANK 76 00:03:18,280 --> 00:03:20,680 YOU SO MUCH FOR BEING WITH US 77 00:03:20,680 --> 00:03:20,880 TODAY. 78 00:03:20,880 --> 00:03:24,360 >> THANK YOU VERY MUCH FOR THE 79 00:03:24,360 --> 00:03:26,680 KIND INTRODUCTION. 80 00:03:26,680 --> 00:03:28,120 I WAS AMUSED, ONE GETS CME 81 00:03:28,120 --> 00:03:29,160 MEDICAL CREDIT FOR LISTENING TO 82 00:03:29,160 --> 00:03:31,120 A TALK ON BIRD VOCALIZATION. 83 00:03:31,120 --> 00:03:33,320 I'M NOT SURE WHY THAT'S 84 00:03:33,320 --> 00:03:35,200 IMPORTANT FOR CONTINUING MEDICAL 85 00:03:35,200 --> 00:03:36,360 EDUCATION. 86 00:03:36,360 --> 00:03:39,000 BUT IN ANY CASE, I'M TALKING TO 87 00:03:39,000 --> 00:03:40,640 YOU RIGHT NOW WITH MY THROAT 88 00:03:40,640 --> 00:03:46,040 THAT IS TO SAY MY LARYNX. 89 00:03:46,040 --> 00:03:48,160 MOST TETRAPODS, ANIMALS THAT 90 00:03:48,160 --> 00:03:50,760 CRAWL ON LAND, USE THE LARYNX TO 91 00:03:50,760 --> 00:03:53,160 SPEAK, INCLUDING REPTILES LIKE 92 00:03:53,160 --> 00:03:55,360 ALLIGATORS, AMPHIBIANS LIKE 93 00:03:55,360 --> 00:03:56,520 PROGRESSES, ALL MAMMALS, 94 00:03:56,520 --> 00:03:57,560 ULTRASONIC SQUEAK A MOUSE MAKES 95 00:03:57,560 --> 00:03:58,960 IS WITH THE LARYNX. 96 00:03:58,960 --> 00:04:01,600 WE'RE ALL SPEAKING WITH OUR 97 00:04:01,600 --> 00:04:02,160 LARYNX. 98 00:04:02,160 --> 00:04:07,080 LARYNX IS THE VOICE BOX IN THE 99 00:04:07,080 --> 00:04:07,640 THROAT. 100 00:04:07,640 --> 00:04:10,360 HAS VOCAL CORDS SHOWN IN THE 101 00:04:10,360 --> 00:04:13,560 REGIONS IN GREEN, CROSS-SECTION. 102 00:04:13,560 --> 00:04:14,760 BIRDS HAVE A LARYNX, IT'S AN 103 00:04:14,760 --> 00:04:16,960 IMPORTANT PART OF THEIR ANATOMY 104 00:04:16,960 --> 00:04:17,960 FOR REGULATING AIR FLOW IN AND 105 00:04:17,960 --> 00:04:20,520 OUT OF THEIR MOUTH. 106 00:04:20,520 --> 00:04:22,080 THERE'S NO VIBRATORY TISSUE, 107 00:04:22,080 --> 00:04:24,880 DON'T HAVE VOCAL CORDS IN THE 108 00:04:24,880 --> 00:04:25,360 THROAT. 109 00:04:25,360 --> 00:04:26,760 INSTEAD, PERHAPS SURPRISINGLY, 110 00:04:26,760 --> 00:04:29,000 BIRDS HAVE EVOLVED A SEPARATE 111 00:04:29,000 --> 00:04:32,600 ORGAN, THE SYRINX, IN THE CHEST 112 00:04:32,600 --> 00:04:35,160 AT THE JUNCTION HERE BETWEEN THE 113 00:04:35,160 --> 00:04:38,720 TRACHEA AND BRONCHI, IN THE 114 00:04:38,720 --> 00:04:39,760 CHEST WHERE THEY HAVE A 115 00:04:39,760 --> 00:04:43,720 CARTILAGE BOX AS IN THE LARYNX 116 00:04:43,720 --> 00:04:46,720 AND THAT LOCATION THEY PUT VOCAL 117 00:04:46,720 --> 00:04:46,920 FOLDS. 118 00:04:46,920 --> 00:04:50,080 THE SYRINX, AS AN ASIDE, WAS THE 119 00:04:50,080 --> 00:04:53,480 NAME COINED BY THOMAS HUXLEY IN 120 00:04:53,480 --> 00:04:56,600 1872, AND HE NAMED THE SYRINX 121 00:04:56,600 --> 00:05:00,280 FROM GREEK MYTHOLOGY, SYRINX WAS 122 00:05:00,280 --> 00:05:02,680 A WATER NYMPH WHO PAN WAS 123 00:05:02,680 --> 00:05:05,440 ENAMORED OF, PAN TRIED TO TRIED 124 00:05:05,440 --> 00:05:16,040 HER IN THE RIVER, TURNING HER 125 00:05:16,040 --> 00:05:18,440 TO REEDS, THE PLUCKED HER AND 126 00:05:18,440 --> 00:05:21,760 MADE THE FIRST PAN PIPES, IN 127 00:05:21,760 --> 00:05:23,280 GREEK, THE SYRINX, MAKES 128 00:05:23,280 --> 00:05:24,360 BEAUTIFUL SOUNDS, A SIMILAR 129 00:05:24,360 --> 00:05:27,080 SHAPE, HENCE THE NAME FROM 130 00:05:27,080 --> 00:05:27,360 HUXLEY. 131 00:05:27,360 --> 00:05:30,240 THE SYRINX IS SHOWN IN THIS 132 00:05:30,240 --> 00:05:31,480 BIRD, IN THIS PARTICULAR BIRD, 133 00:05:31,480 --> 00:05:32,680 IS NOT THE SAME IN ALL BIRDS. 134 00:05:32,680 --> 00:05:34,360 THIS IS SOMETHING I'M NOT GOING 135 00:05:34,360 --> 00:05:38,560 TO ADDRESS TODAY BUT IT'S AN 136 00:05:38,560 --> 00:05:38,760 ASIDE. 137 00:05:38,760 --> 00:05:42,560 MY LARYNX, OF AN ALLIGATOR, OF A 138 00:05:42,560 --> 00:05:44,440 FROG, ALL PRETTY MUCH LOOK THE 139 00:05:44,440 --> 00:05:44,760 SAME. 140 00:05:44,760 --> 00:05:46,600 THE SYRINX HOWEVER CAN BE 141 00:05:46,600 --> 00:05:47,960 DRAMATICALLY DIFFERENT FROM BIRD 142 00:05:47,960 --> 00:05:50,200 TO BIRD. 143 00:05:50,200 --> 00:05:52,320 THIS CORRELATES WITH THEM MAKING 144 00:05:52,320 --> 00:05:53,840 DIFFERENT SOUNDS. 145 00:05:53,840 --> 00:05:55,000 A WOOD PIGEON SOUNDS LIKE THIS 146 00:05:55,000 --> 00:06:00,840 ... 147 00:06:00,840 --> 00:06:02,080 WHITE THROATED SPARROW SOUNDS 148 00:06:02,080 --> 00:06:06,760 LIKE THIS ... 149 00:06:06,760 --> 00:06:09,760 VERY DIFFERENT STRUCTURES OF THE 150 00:06:09,760 --> 00:06:10,120 SYRINX. 151 00:06:10,120 --> 00:06:10,600 INCLUDING, FOR EXAMPLE, 152 00:06:10,600 --> 00:06:13,520 EVOLUTION OF DIFFERENT SETS OF 153 00:06:13,520 --> 00:06:15,720 MUSCLES TO REGULATE AND PRODUCE 154 00:06:15,720 --> 00:06:16,560 DIFFERENT SOUNDS. 155 00:06:16,560 --> 00:06:17,680 AND DIFFERENT LOCATIONS OF THE 156 00:06:17,680 --> 00:06:19,960 VOCAL FOLDS, EITHER ON THE 157 00:06:19,960 --> 00:06:21,400 TRACHEA SIDE OF THE SYRINX, WITH 158 00:06:21,400 --> 00:06:24,920 A SINGLE PAIR, OTHER THAN -- OR 159 00:06:24,920 --> 00:06:28,520 TWO PAIRS IN THE CASE OF SONG 160 00:06:28,520 --> 00:06:29,760 BIRDS, SOME GROUPS, PARROTS AS 161 00:06:29,760 --> 00:06:29,960 WELL. 162 00:06:29,960 --> 00:06:32,600 THE REASON HAVING TWO PAIRS IS 163 00:06:32,600 --> 00:06:34,800 INTERESTING IS HERE'S A WOOD 164 00:06:34,800 --> 00:06:38,760 THRUSH, ITS SOUND ... 165 00:06:38,760 --> 00:06:40,840 BEAUTIFUL COMPLEX SOUNDS. 166 00:06:40,840 --> 00:06:43,840 THE WOOD THRUSH MAKES THESE 167 00:06:43,840 --> 00:06:45,040 SOUNDS SINGING SEPARATELY FROM 168 00:06:45,040 --> 00:06:49,000 THE TWO VOCAL CORDS. 169 00:06:49,000 --> 00:06:52,520 IT CAN HARMONIZE WITH ITSELF, 170 00:06:52,520 --> 00:06:54,640 HARMONIZING HITTING DIFFERENT 171 00:06:54,640 --> 00:06:57,760 NOTES, SLOWING IT DOWN ... 172 00:06:57,760 --> 00:06:59,160 SO IT'S A BEAUTIFUL AND DIVERSE 173 00:06:59,160 --> 00:06:59,400 ORGAN. 174 00:06:59,400 --> 00:07:02,560 THERE IS WORK IN MY LAB TO TRY 175 00:07:02,560 --> 00:07:03,240 TO UNDERSTAND DIVERSIFICATION OF 176 00:07:03,240 --> 00:07:12,000 THE SHIRKS. 177 00:07:12,000 --> 00:07:12,560 SYRINX. 178 00:07:12,560 --> 00:07:13,760 REPTILES AND AMPHIBIANS HAVE A 179 00:07:13,760 --> 00:07:18,360 LARYNX, AS WE DO AS WELL. 180 00:07:18,360 --> 00:07:21,040 THAT'S REPRESENTED BY THIS BLACK 181 00:07:21,040 --> 00:07:23,040 DOT AND THE BARS MEAN IT'S A 182 00:07:23,040 --> 00:07:24,280 FUNCTIONAL LARYNX THAT SINGS. 183 00:07:24,280 --> 00:07:27,760 THEY DO NOT HAVE A SYRINX. 184 00:07:27,760 --> 00:07:31,280 MODERN BIRDS HAVE A LARYNX DOES 185 00:07:31,280 --> 00:07:33,560 NOT SING BUT A SYRINX THAT DOES 186 00:07:33,560 --> 00:07:33,760 SING. 187 00:07:33,760 --> 00:07:37,240 BETWEEN CROWN BIRDS AND 188 00:07:37,240 --> 00:07:38,760 REPTILES, IN THIS NON-AVIAN 189 00:07:38,760 --> 00:07:40,360 DINOSAUR LINEAGE, SYRINX MUST 190 00:07:40,360 --> 00:07:41,000 HAVE EVOLVED. 191 00:07:41,000 --> 00:07:42,400 IT'S INTERESTING TO THINK ABOUT 192 00:07:42,400 --> 00:07:44,760 HOW IT EVOLVED. 193 00:07:44,760 --> 00:07:46,000 THAT IS, TWO POSSIBILITIES. 194 00:07:46,000 --> 00:07:48,720 EITHER YOU FIRST LOST THE LARYNX 195 00:07:48,720 --> 00:07:52,000 AND YOU HAD A QUIET ANIMAL THAT 196 00:07:52,000 --> 00:07:55,960 HAD TO INVENT THE SYRINX TO TALK 197 00:07:55,960 --> 00:07:57,800 OR FUNCTIONAL OVERLAP, AT THE 198 00:07:57,800 --> 00:07:59,360 SAME TIME, AND WHY YOU HAD THE 199 00:07:59,360 --> 00:08:00,400 TRANSITION FROM ONE TO ANOTHER. 200 00:08:00,400 --> 00:08:01,480 THIS IS SOMETHING WE'RE 201 00:08:01,480 --> 00:08:04,960 EXPLORING WITH A COLLEAGUE OF 202 00:08:04,960 --> 00:08:07,200 OURS, JULIA CLARK, UNIVERSITY OF 203 00:08:07,200 --> 00:08:08,840 TEXAS AUSTIN, PALEONTOLOGIST, 204 00:08:08,840 --> 00:08:13,000 TRYING TO FIND EVIDENCE FOR 205 00:08:13,000 --> 00:08:14,760 EARLIEST SYRINXES, ESPECIALLY IN 206 00:08:14,760 --> 00:08:15,720 A DINOSAUR LINEAGE. 207 00:08:15,720 --> 00:08:20,640 AS FAR BACK AS SHE'S GOTTEN SO 208 00:08:20,640 --> 00:08:26,360 FAR HOWEVER, IT'S A DEFINITIVE 209 00:08:26,360 --> 00:08:30,880 CROWN FOWL, IT HAS A SYRINX, 210 00:08:30,880 --> 00:08:33,920 LIKE DUCKS AND GEESE. 211 00:08:33,920 --> 00:08:36,360 TRYING TO UNDERSTAND FROM A 212 00:08:36,360 --> 00:08:38,560 DEVELOPMENTAL STANDPOINT, HOW DO 213 00:08:38,560 --> 00:08:40,360 YOU MAKE A NOVEL STRUCTURE? 214 00:08:40,360 --> 00:08:42,760 THE SYRINX IS AN EXAMPLE OF 215 00:08:42,760 --> 00:08:43,120 SOMETHING NEW. 216 00:08:43,120 --> 00:08:47,560 IT'S NOT LIKE A BIRD'S WING 217 00:08:47,560 --> 00:08:49,160 WHICH IS HOMOLOGOUS TO 218 00:08:49,160 --> 00:08:50,520 NON-FLYING ANIMAL'S LIMB. 219 00:08:50,520 --> 00:08:53,200 IN THIS CASE EVOLUTION OF 220 00:08:53,200 --> 00:08:54,120 STRUCTURE, YES IT'S BUILT ON 221 00:08:54,120 --> 00:08:56,960 PARTS THAT WERE ALREADY THERE 222 00:08:56,960 --> 00:08:59,080 BUT NO PREEXISTING SYRINX, NO 223 00:08:59,080 --> 00:09:00,600 PREEXISTING VALVES, SO WHERE DID 224 00:09:00,600 --> 00:09:01,560 IT COME FROM? 225 00:09:01,560 --> 00:09:03,880 SO WE'RE GOING TO TALK ABOUT IT 226 00:09:03,880 --> 00:09:05,200 IN TWO PARTS. 227 00:09:05,200 --> 00:09:07,400 FIRST, THE BUILDING OF THE VOICE 228 00:09:07,400 --> 00:09:09,160 BOX, THE CARTILAGE BOX ITSELF. 229 00:09:09,160 --> 00:09:12,120 AND THEN HOW YOU GET THE VOCAL 230 00:09:12,120 --> 00:09:13,400 FOLDS WITHIN IT. 231 00:09:13,400 --> 00:09:17,360 SO, ONE WAY YOU CAN IMAGINE YOU 232 00:09:17,360 --> 00:09:19,120 GET THIS SPECIALIZED SYRINX 233 00:09:19,120 --> 00:09:23,960 WOULD BE TO BUILD ON THE 234 00:09:23,960 --> 00:09:26,200 PREEXISTING CARTILAGE RINGS IN 235 00:09:26,200 --> 00:09:27,840 THE TRACHEA AND BRONCHI, IN THE 236 00:09:27,840 --> 00:09:32,160 SYRINX THEY ARE THICKER AND 237 00:09:32,160 --> 00:09:36,000 CHANGE SHAPE SOME, BUT IMAGINE 238 00:09:36,000 --> 00:09:38,440 LAY DOWN A CONTINUOUS PATTERN, 239 00:09:38,440 --> 00:09:40,560 MODIFY SUBSEQUENTLY TO GET 240 00:09:40,560 --> 00:09:42,520 STRUCTURE THAT'S APPROPRIATE FOR 241 00:09:42,520 --> 00:09:44,080 HOUSING VOCAL CORDS. 242 00:09:44,080 --> 00:09:45,280 SO, TO THINK ABOUT THAT ONE 243 00:09:45,280 --> 00:09:46,600 WANTS TO TAKE A STEP BACK AND 244 00:09:46,600 --> 00:09:48,960 SAY HOW DO YOU GET CARTILAGE 245 00:09:48,960 --> 00:09:51,120 RINGS TO BEGIN WITH? 246 00:09:51,120 --> 00:09:53,080 AND THERE'S BEEN A LOT OF WORK 247 00:09:53,080 --> 00:09:55,360 DONE ON THE DEVELOPMENT OF THE 248 00:09:55,360 --> 00:09:58,120 AIRWAY HOW YOU ACTUALLY GET 249 00:09:58,120 --> 00:10:00,280 RING, NON-RING, RING, NOT RING, 250 00:10:00,280 --> 00:10:01,000 NOT DEFINED DEVELOPMENTALLY 251 00:10:01,000 --> 00:10:03,000 PREVIOUSLY BUT WE CAN THINK 252 00:10:03,000 --> 00:10:04,120 ABOUT IT FROM THEORETICAL 253 00:10:04,120 --> 00:10:04,840 STANDPOINT. 254 00:10:04,840 --> 00:10:08,120 ONE WAY OF MODELING HOW YOU CAN 255 00:10:08,120 --> 00:10:09,120 GET THIS SORT OF PARALLEL 256 00:10:09,120 --> 00:10:11,440 STRIPES IS THROUGH A MODEL OF 257 00:10:11,440 --> 00:10:13,840 SOMETHING LIKE A TOURING SYSTEM. 258 00:10:13,840 --> 00:10:15,720 SO, WITHOUT GOING INTO DETAILS 259 00:10:15,720 --> 00:10:19,320 ABOUT A TOURING MECHANISM TODAY, 260 00:10:19,320 --> 00:10:34,200 SUFFICE IT TO SAY THAT TURING 261 00:10:34,200 --> 00:10:38,240 MECHANIC, ONE ACTIVATOR, ONE 262 00:10:38,240 --> 00:10:39,640 INHIBITORS, INDUCING EXPRESSION 263 00:10:39,640 --> 00:10:41,600 OF INHIBITOR WHICH INHIBITS THE 264 00:10:41,600 --> 00:10:42,640 PROGRAM. 265 00:10:42,640 --> 00:10:45,720 JUST THE TWO MOLECULES COMBINED 266 00:10:45,720 --> 00:10:49,880 CAN GIVE PERIODIC PATTERNS, 267 00:10:49,880 --> 00:10:57,600 GENERATE A RANGE OF SHAPES IN 268 00:10:57,600 --> 00:10:59,120 SILICO THAT MIMICS NATURE, 269 00:10:59,120 --> 00:11:02,560 INCLUDING PARABLE STRIPES. 270 00:11:02,560 --> 00:11:03,680 PARABLE STRIPES. 271 00:11:03,680 --> 00:11:07,120 THAT'S WHAT HAPPENS AT THE 272 00:11:07,120 --> 00:11:07,360 JUNCTION. 273 00:11:07,360 --> 00:11:10,320 WHEN YOU HAVE THE COLLISION OF A 274 00:11:10,320 --> 00:11:13,480 TURING PATTERN DOWN THE TRACHEA 275 00:11:13,480 --> 00:11:15,520 AND TURING PATTERNS COMING UP 276 00:11:15,520 --> 00:11:16,720 THE BRONCHI. 277 00:11:16,720 --> 00:11:19,560 YOU MODEL, YOU GET A MESS. 278 00:11:19,560 --> 00:11:20,640 YOU DON'T GET CLEAN STRIPES AT 279 00:11:20,640 --> 00:11:22,360 THE JUNCTION. 280 00:11:22,360 --> 00:11:25,920 IF YOU LOOK AT THE TRACHEAL 281 00:11:25,920 --> 00:11:26,920 BRONCHIAL JUNCTION IN HUMANS OR 282 00:11:26,920 --> 00:11:28,680 MICE THAT'S WHAT YOU SEE. 283 00:11:28,680 --> 00:11:32,160 THIS FIGURE OVER HERE ON THE 284 00:11:32,160 --> 00:11:37,160 LEFT TAKEN FROM AN 1891 285 00:11:37,160 --> 00:11:39,560 MONOGRAPH, INTERESTING PAPER, 286 00:11:39,560 --> 00:11:42,120 ENTIRE MONOGRAPH IS 86 HUMAN 287 00:11:42,120 --> 00:11:44,160 CADAVER ANALYSES DRAWING JUST 288 00:11:44,160 --> 00:11:45,680 THE CADAVER'S TRACHEA AND 289 00:11:45,680 --> 00:11:47,040 BRONCHIAL JUNCTION. 290 00:11:47,040 --> 00:11:50,280 THESE ARE NOT MEN WEARING WEIRD 291 00:11:50,280 --> 00:11:51,840 GYM SHORTS. 292 00:11:51,840 --> 00:11:53,920 THESE ARE BRONCHI IN THE 293 00:11:53,920 --> 00:11:55,520 TRACHEA, YOU CAN SEE THE POINT 294 00:11:55,520 --> 00:11:56,960 THEY WERE MAKING WAS NO TWO 295 00:11:56,960 --> 00:11:57,640 JUNCTIONS ARE ALIKE. 296 00:11:57,640 --> 00:11:59,680 WE ALL HAVE RINGS ABOVE AND 297 00:11:59,680 --> 00:12:01,080 BELOW, BUT THE JUNCTION YOU GET 298 00:12:01,080 --> 00:12:01,560 A MESS. 299 00:12:01,560 --> 00:12:03,320 WE GET THE SAME THING IN THE 300 00:12:03,320 --> 00:12:03,760 MOUSE. 301 00:12:03,760 --> 00:12:05,400 REMINISCENT OF WHAT YOU GET 302 00:12:05,400 --> 00:12:05,720 HERE. 303 00:12:05,720 --> 00:12:07,480 THAT'S FINE IF ALL YOU'RE TRYING 304 00:12:07,480 --> 00:12:09,000 DO IS GET CARTILAGE SUPPORT FOR 305 00:12:09,000 --> 00:12:09,360 AIRWAY. 306 00:12:09,360 --> 00:12:11,160 IF YOU WANT TO MAKE A CAREFUL 307 00:12:11,160 --> 00:12:14,480 STRUCTURE TO SUPPORT SINGING OR 308 00:12:14,480 --> 00:12:15,240 SPEAKING, VOICE BOX, YOU CAN'T 309 00:12:15,240 --> 00:12:17,200 AFFORD TO HAVE THIS TYPE OF MESS 310 00:12:17,200 --> 00:12:18,680 GOING ON. 311 00:12:18,680 --> 00:12:21,160 SO HOW DO YOU AVOID THAT? 312 00:12:21,160 --> 00:12:24,200 SO, A POSTDOC IN MY LAB EVAN 313 00:12:24,200 --> 00:12:25,400 KINGSLEY DECIDED TO LOOK INTO 314 00:12:25,400 --> 00:12:30,280 THAT AND WATCHED THE ANTOGENY OF 315 00:12:30,280 --> 00:12:32,960 THE RINGS OVER TIME. 316 00:12:32,960 --> 00:12:35,960 YOU HAVE AN AIRWAY, TRACHEA 317 00:12:35,960 --> 00:12:36,960 BRONCHIAL JUNCTION, BASICALLY NO 318 00:12:36,960 --> 00:12:37,160 RINGS. 319 00:12:37,160 --> 00:12:38,640 A DAY LATER THERE'S THE START OF 320 00:12:38,640 --> 00:12:39,160 RINGS. 321 00:12:39,160 --> 00:12:40,760 DAY LATER YOU HAVE THE RINGS. 322 00:12:40,760 --> 00:12:44,840 THEY BASICALLY ALL COME UP AT 323 00:12:44,840 --> 00:12:45,040 ONCE. 324 00:12:45,040 --> 00:12:50,880 THAT CONTRAST, I SHOULD SAY 325 00:12:50,880 --> 00:12:53,560 UNLIKE SOMITS ADDED ONE AT A 326 00:12:53,560 --> 00:12:55,320 TIME THIS SEGMENTATION IS VERY 327 00:12:55,320 --> 00:12:57,760 CONSISTENT WITH THE REACTION TO 328 00:12:57,760 --> 00:13:00,920 FUSION MECHANISM THAT TURING WAS 329 00:13:00,920 --> 00:13:02,520 PROPOSING. 330 00:13:02,520 --> 00:13:07,000 BUT YOU GET A DIFFERENT 331 00:13:07,000 --> 00:13:08,360 ONTOLOGICAL PATTERN IN THE 332 00:13:08,360 --> 00:13:10,760 CHICKEN, OR ANY OTHER BIRD, YOU 333 00:13:10,760 --> 00:13:12,480 FIND INITIALLY THERE'S NO 334 00:13:12,480 --> 00:13:13,680 CARTILAGE, BUT CARTILAGE OF THE 335 00:13:13,680 --> 00:13:16,000 SYRINX COMES UP FIRST. 336 00:13:16,000 --> 00:13:18,760 FIRST YOU DEVELOP THE SYRINGEAL 337 00:13:18,760 --> 00:13:20,600 CARTILAGE, THEN YOU DEVELOP THE 338 00:13:20,600 --> 00:13:21,240 OTHER CARTILAGE. 339 00:13:21,240 --> 00:13:24,720 THIS MAKES PERFECT SENSE. 340 00:13:24,720 --> 00:13:30,120 YOU AVOID HAVING THIS MESS AT 341 00:13:30,120 --> 00:13:31,280 THE INTERSECTION AND THEN BUILD 342 00:13:31,280 --> 00:13:32,520 RINGS ABOVE AND BELOW. 343 00:13:32,520 --> 00:13:35,720 MAKES PERFECT SENSE BUT HOW DO 344 00:13:35,720 --> 00:13:37,360 YOU GET THIS TO DEVELOP BEFORE 345 00:13:37,360 --> 00:13:38,320 THE OTHER RINGS? 346 00:13:38,320 --> 00:13:43,960 TO GET A HANDLE WE DID AN 347 00:13:43,960 --> 00:13:45,080 RNAseq ANALYSIS WHERE WE 348 00:13:45,080 --> 00:13:46,360 COMPARED ALLIGATOR WHERE 349 00:13:46,360 --> 00:13:50,760 EVERYTHING IS COMING UP AT ONCE, 350 00:13:50,760 --> 00:13:51,640 TRACHEOBRONCHIAL JUNCTION WHERE 351 00:13:51,640 --> 00:13:53,160 THE SYRINX WOULD FORM WITH THE 352 00:13:53,160 --> 00:13:57,840 TRACHEA IN BOTH THE MESENCHYME 353 00:13:57,840 --> 00:14:02,600 AND EPITHELIUM, SAME IN CHICKEN, 354 00:14:02,600 --> 00:14:06,680 ENDODERM AND MISODERMAL LAYERS, 355 00:14:06,680 --> 00:14:07,760 WHAT IS NOT DIFFERENTIALLY 356 00:14:07,760 --> 00:14:11,000 EXPRESSED IN THE ALLIGATOR 357 00:14:11,000 --> 00:14:12,240 WHERE PATTERNS ARE THE SAME? 358 00:14:12,240 --> 00:14:17,160 IF YOU DO THAT WHAT YOU FIND 359 00:14:17,160 --> 00:14:18,040 VARIOUS MEMBERS OF THE HEDGE HOG 360 00:14:18,040 --> 00:14:20,080 SIGNALING PATHWAY. 361 00:14:20,080 --> 00:14:24,600 SO YOU CAN LOOK AT THAT, THAT'S 362 00:14:24,600 --> 00:14:27,240 BY RNA ANALYSIS, VERIFIED BY IN 363 00:14:27,240 --> 00:14:27,680 SITU HYBRIDIZATION. 364 00:14:27,680 --> 00:14:29,520 THIS IS A LITTLE BIT CONFUSES, 365 00:14:29,520 --> 00:14:32,680 THE FIRST PANEL HERE, BECAUSE 366 00:14:32,680 --> 00:14:33,520 THE DISSECTION DIDN'T SEPARATE 367 00:14:33,520 --> 00:14:37,200 THE GUT FROM THE TRACHEA. 368 00:14:37,200 --> 00:14:39,400 SO THE ENTIRE AIRWAY FORMS THIS 369 00:14:39,400 --> 00:14:40,680 BUDDING OFF OF THE GUT. 370 00:14:40,680 --> 00:14:43,600 YOU CAN SEE BEHIND IT THE GUT. 371 00:14:43,600 --> 00:14:45,040 SO THIS STRIPE HERE, THIS DOWN 372 00:14:45,040 --> 00:14:47,560 HERE ARE EXPRESSION IN THE GUT. 373 00:14:47,560 --> 00:14:49,880 IN THE AIRWAY, YOU HAVE A 374 00:14:49,880 --> 00:14:51,400 CONTINUOUS EXPRESSION IN THE 375 00:14:51,400 --> 00:14:53,160 TRACHEA AT THE JUNCTION AND 376 00:14:53,160 --> 00:14:59,400 BRONCHI OF SONIC HEDGE HOG. 377 00:14:59,400 --> 00:15:00,600 THEN IT DISAPPEARS, SONIC 378 00:15:00,600 --> 00:15:02,120 HEDGEHOG GOES AWAY WHERE THE 379 00:15:02,120 --> 00:15:06,480 SYRINX IS GOING TO FORM AND GOES 380 00:15:06,480 --> 00:15:07,800 AWAY EVERYWHERE ELSE, 381 00:15:07,800 --> 00:15:09,920 TIMING-WISE CORRELATES WELL. 382 00:15:09,920 --> 00:15:11,720 FIRST SONIC GOES AWAY. 383 00:15:11,720 --> 00:15:13,360 THEN YOU GET CARTILAGES AT THE 384 00:15:13,360 --> 00:15:13,680 SYRINX. 385 00:15:13,680 --> 00:15:14,840 THEN SONIC GOES AWAY IN THE REST 386 00:15:14,840 --> 00:15:15,400 OF THE TUBE. 387 00:15:15,400 --> 00:15:18,160 THEN YOU GET THE REST OF THE 388 00:15:18,160 --> 00:15:19,920 TRACHEA, REST OF THE CARTILAGES. 389 00:15:19,920 --> 00:15:20,880 THAT'S A CORRELATION. 390 00:15:20,880 --> 00:15:23,200 TO SEE WHERE THE SONIC ACTSES, 391 00:15:23,200 --> 00:15:25,040 THE ARGUMENT IS SONIC IS 392 00:15:25,040 --> 00:15:27,440 INHIBITING FORMATION OF THE 393 00:15:27,440 --> 00:15:28,400 CARTILAGE, SONIC DISAPPEARS, YOU 394 00:15:28,400 --> 00:15:29,760 GET CARTILAGE. 395 00:15:29,760 --> 00:15:32,240 TO TEST THAT, WENT IN VITRO. 396 00:15:32,240 --> 00:15:34,960 YOU CAN CULTURE AVIAN AIRWAY 397 00:15:34,960 --> 00:15:37,680 FROM STAGE WHEN THERE IS NO CART 398 00:15:37,680 --> 00:15:40,440 RANCH, TO AFTER THE STAGE, FIVE 399 00:15:40,440 --> 00:15:43,200 DAYS LATER, CARTILAGE IS FORMED, 400 00:15:43,200 --> 00:15:45,440 FORMED PERFECTLY AS IN VIVO. 401 00:15:45,440 --> 00:15:51,200 YOU CAN PUT IN BEADS, SONIC 402 00:15:51,200 --> 00:15:52,240 HEDGEHOG OR OTHER PROTEINS, AND 403 00:15:52,240 --> 00:15:54,120 SAY WHAT DOES THAT DO THE TO THE 404 00:15:54,120 --> 00:15:55,000 PATTERN. 405 00:15:55,000 --> 00:15:56,960 WHAT YOU FIND IS IF YOU PUT IN A 406 00:15:56,960 --> 00:15:59,120 CONTROL BEAD HERE IN 407 00:15:59,120 --> 00:15:59,960 CROSS-SECTION OF THE CARTILAGES, 408 00:15:59,960 --> 00:16:01,400 THE SYRINX, IF YOU PUT IN SONIC 409 00:16:01,400 --> 00:16:06,360 ON THE SIDE WITH THE SONIC BEAD 410 00:16:06,360 --> 00:16:07,480 CARTAGES DISAPPEAR. 411 00:16:07,480 --> 00:16:09,480 OR DIFFERENT TYPE EXPERIMENT 412 00:16:09,480 --> 00:16:15,920 USING AGONIST TO BLOCK HEDGEHOG 413 00:16:15,920 --> 00:16:16,600 SIGNALING, BLOCK GLOBALLY, 414 00:16:16,600 --> 00:16:19,600 CARTILAGE FAILS TO FORM 415 00:16:19,600 --> 00:16:20,280 GLOBALLY. 416 00:16:20,280 --> 00:16:21,640 NOW, IF YOU APPLY SONIC HEDGEHOG 417 00:16:21,640 --> 00:16:22,920 EARLY WHEN THE SYRINX IS 418 00:16:22,920 --> 00:16:26,520 FORMING, IF YOU LET THE SYRINX 419 00:16:26,520 --> 00:16:30,160 FORM AND APPLY HEDGEHOG AT LATER 420 00:16:30,160 --> 00:16:31,160 STAGE, WHERE IT'S GOING THROUGH 421 00:16:31,160 --> 00:16:34,400 THE TRACHEA, NOW YOU SEE THE 422 00:16:34,400 --> 00:16:36,840 SYRINX HAS BEEN LAID DOWN 423 00:16:36,840 --> 00:16:41,360 CONTINUOUS TO FORM, TRACHEAL 424 00:16:41,360 --> 00:16:43,720 RINGS NO LONGER FORM. 425 00:16:43,720 --> 00:16:46,160 IF HEDGEHOG IS THERE YOU DON'T 426 00:16:46,160 --> 00:16:47,320 GET THE CARTILAGE RINGS. 427 00:16:47,320 --> 00:16:48,080 ALL RIGHT. 428 00:16:48,080 --> 00:16:51,480 WE HAVE A BIT OF A CLUE AS TO 429 00:16:51,480 --> 00:16:57,040 HOW YOU GET THESE CARTILAGE 430 00:16:57,040 --> 00:16:58,680 RINGS TO FORM WITHOUT INTERFERES 431 00:16:58,680 --> 00:17:01,000 FROM THE TURING PATTERN BY 432 00:17:01,000 --> 00:17:02,320 TAKING THIS INHIBITOR, SONIC, 433 00:17:02,320 --> 00:17:05,400 REMOVING FIRST HERE AND THEN 434 00:17:05,400 --> 00:17:07,640 EVERYWHERE ELSE. 435 00:17:07,640 --> 00:17:09,600 WHY IS SONIC HANGING AROUND AS 436 00:17:09,600 --> 00:17:12,400 INHIBITOR IN THE FIRST PLACE, 437 00:17:12,400 --> 00:17:15,600 ANCESTRAL BEFORE THE EVOLUTION 438 00:17:15,600 --> 00:17:17,600 OF THE SYRINX, WHAT WAS IT DOING 439 00:17:17,600 --> 00:17:18,760 ON AN ALLIGATOR? 440 00:17:18,760 --> 00:17:21,920 A CLUE, OTHER THAN BEING A 441 00:17:21,920 --> 00:17:24,240 TIMING MECHANISM, COMES FROM 442 00:17:24,240 --> 00:17:30,400 LOOKING AT THE EXPRESSION OF 443 00:17:30,400 --> 00:17:33,520 HEDGEHOG, IN SECTION. 444 00:17:33,520 --> 00:17:35,160 IF YOU SECTION THROUGH, 445 00:17:35,160 --> 00:17:37,640 SECTIONING THROUGH AT THE LEVEL 446 00:17:37,640 --> 00:17:41,760 OF SYRINX, AT THE LEVEL OF THE 447 00:17:41,760 --> 00:17:43,600 TRACHEA, SONIC IS EXPRESSED IN 448 00:17:43,600 --> 00:17:46,000 THE STRIPE, IT'S ACTUALLY ONLY 449 00:17:46,000 --> 00:17:48,320 EXPRESSED IN CROSS-SECTION IN 450 00:17:48,320 --> 00:17:50,040 THE DORSAL MOST ASPECT OF THE 451 00:17:50,040 --> 00:17:50,520 TRACHEA. 452 00:17:50,520 --> 00:17:55,560 HERE IS THE TRACHEAL ENDODERM. 453 00:17:55,560 --> 00:18:03,600 DORSAL MOST EXPRESSES SONIC, 454 00:18:03,600 --> 00:18:04,400 MESODERM, GRADIENT, HIGH 455 00:18:04,400 --> 00:18:10,720 PATCHED, PATCH EXTENDS TO THE BOTTOM. 456 00:18:10,720 --> 00:18:14,320 SAME TRUE ON BRONCHI, DORSAL, 457 00:18:14,320 --> 00:18:14,920 NOT VENTRAL. 458 00:18:14,920 --> 00:18:17,600 WHY WOULD YOU HAVE A GRADIENT IN 459 00:18:17,600 --> 00:18:18,240 THIS MANNER? 460 00:18:18,240 --> 00:18:20,320 WELL, LET'S GO BACK TO THINKING 461 00:18:20,320 --> 00:18:21,760 ABOUT TURING MECHANISMS AGAIN, I 462 00:18:21,760 --> 00:18:23,920 WAS FLIPPANT WHEN I TALKED ABOUT 463 00:18:23,920 --> 00:18:25,240 IT BEFORE. 464 00:18:25,240 --> 00:18:26,560 THEY ARE GREAT GENERATING ALL 465 00:18:26,560 --> 00:18:29,520 SORTS OF PATTERNS FOUND IN 466 00:18:29,520 --> 00:18:31,480 NATURE. 467 00:18:31,480 --> 00:18:38,240 IT CAN FORM MAZES, DOTS, 468 00:18:38,240 --> 00:18:38,800 CIRCLES, POLYGONS. 469 00:18:38,800 --> 00:18:41,000 ONE THING THEY ARE NOT VERY GOOD 470 00:18:41,000 --> 00:18:44,960 AT IS FORMING PARALLEL STRIPES. 471 00:18:44,960 --> 00:18:48,960 TOM HITCHCOCK UNIVERSITY OF 472 00:18:48,960 --> 00:18:50,960 ABERDEEN SHOWED IN 2015 TO GET A 473 00:18:50,960 --> 00:18:53,480 TURING PATTERN TO FORM REAL 474 00:18:53,480 --> 00:18:55,680 STRIPES, TRUE STRIPES, REQUIRES 475 00:18:55,680 --> 00:18:59,560 SOMETHING ELSE. 476 00:18:59,560 --> 00:19:01,760 THEY FORM PARALLEL-ISH LINES BUT 477 00:19:01,760 --> 00:19:03,680 FOR TIGHT STRIPES FOR EXAMPLE 478 00:19:03,680 --> 00:19:07,160 WITH A GRADIENT IN SILICO, 479 00:19:07,160 --> 00:19:08,280 PARAMETER GRADIENT, THEORETICAL, 480 00:19:08,280 --> 00:19:09,400 JUST A GRADIENT OF SOMETHING 481 00:19:09,400 --> 00:19:11,760 ELSE TO ORIENT THOSE STRIPES. 482 00:19:11,760 --> 00:19:15,200 SO WE ASKED TOM IF HE COULD 483 00:19:15,200 --> 00:19:16,480 MODEL IN THREE DIMENSIONS WHAT'S 484 00:19:16,480 --> 00:19:17,320 HAPPENING IN TWO. 485 00:19:17,320 --> 00:19:18,200 YOU SEE THIS. 486 00:19:18,200 --> 00:19:21,520 AS IN THE TWO DIMENSIONS, THREE 487 00:19:21,520 --> 00:19:22,760 DIMENSIONALLY NO MATTER HOW YOU 488 00:19:22,760 --> 00:19:24,600 TWEAK THE PARAMETERS IT'S 489 00:19:24,600 --> 00:19:25,520 IMPOSSIBLE TO GET REAL PARALLEL 490 00:19:25,520 --> 00:19:28,600 STRIPES UNLESS YOU PUT IN A 491 00:19:28,600 --> 00:19:28,880 GRADIENT. 492 00:19:28,880 --> 00:19:31,000 PARAMETER GRADIENT, IF YOU PUT 493 00:19:31,000 --> 00:19:32,720 IN A STEEP, STEEP GRADIENT, YOU 494 00:19:32,720 --> 00:19:34,080 GET REALLY NICE PARALLEL 495 00:19:34,080 --> 00:19:34,320 STRIPES. 496 00:19:34,320 --> 00:19:38,120 IF YOU HAVE A SHALLOWER 497 00:19:38,120 --> 00:19:39,800 GRADIENT, STILL GIVES YOU 498 00:19:39,800 --> 00:19:42,360 STRIPES BUT THEY GET BRANCHING 499 00:19:42,360 --> 00:19:43,280 FORMS, STRIPES WITH DEFECTS. 500 00:19:43,280 --> 00:19:47,400 THAT'S GOING TO BE IMPORTANT A 501 00:19:47,400 --> 00:19:50,120 COUPLE SLIDES FROM NOW. 502 00:19:50,120 --> 00:19:52,480 A FLAT GRADIENT GIVES YOU 503 00:19:52,480 --> 00:19:53,160 DEFECTIVE STRIPES, STEEP 504 00:19:53,160 --> 00:19:54,720 GRADIENT GIVES YOU PERFECT 505 00:19:54,720 --> 00:19:54,960 STRIPES. 506 00:19:54,960 --> 00:19:57,640 SO IS THERE REALLY A GRADIENT 507 00:19:57,640 --> 00:19:58,800 WITH HEDGEHOG IN THE DEVELOPING 508 00:19:58,800 --> 00:20:00,040 TRACHEA OF THE CHICK? 509 00:20:00,040 --> 00:20:02,360 THERE IS. 510 00:20:02,360 --> 00:20:07,520 IF YOU'RE A SONIC HEDGEHOG, I 511 00:20:07,520 --> 00:20:09,200 SHOWED YOU BEFORE, QUANTIFY THAT 512 00:20:09,200 --> 00:20:14,120 GRADIENT AND SHOW FROM DORSAL TO 513 00:20:14,120 --> 00:20:19,320 VENTRAL A NICE GRADIENT. 514 00:20:19,320 --> 00:20:21,480 MOUSE GRADIENT IS FLATTER. 515 00:20:21,480 --> 00:20:23,200 INTRIGUINGLY, WHILE IN THE CHICK 516 00:20:23,200 --> 00:20:25,480 THE STRIPES ARE PERFECT, JUST 517 00:20:25,480 --> 00:20:27,000 ABSOLUTELY PERFECT, AS WE EXPECT 518 00:20:27,000 --> 00:20:29,200 FROM THE STEEP GRADIENT, IN THE 519 00:20:29,200 --> 00:20:32,280 MOUSE AND HUMAN FOR THAT MATTER, 520 00:20:32,280 --> 00:20:34,240 MAMMALS, YOU HAVE THESE PARALLEL 521 00:20:34,240 --> 00:20:36,520 STRIPES BUT YOU HAVE DEFECTS IN 522 00:20:36,520 --> 00:20:38,600 THE TRACHEA AND BRONCHI. 523 00:20:38,600 --> 00:20:41,280 SIMILAR TO WHAT YOU EXPECT FROM 524 00:20:41,280 --> 00:20:42,320 FLATTER GRADIENT. 525 00:20:42,320 --> 00:20:44,600 HOW DO WE ENVISION A FLAT 526 00:20:44,600 --> 00:20:46,640 GRADIENT WORKING TO GIVE YOU 527 00:20:46,640 --> 00:20:48,000 PARALLEL STRIPES? 528 00:20:48,000 --> 00:20:49,840 SO REMEMBER HEDGEHOG IS SHUT 529 00:20:49,840 --> 00:20:51,440 DOWN OVER TIME. 530 00:20:51,440 --> 00:20:53,840 IMAGINE A SITUATION WHERE 531 00:20:53,840 --> 00:20:56,360 INITIALLY HEDGEHOG SHOWN IN RED 532 00:20:56,360 --> 00:20:59,840 IS EXPRESSED IN THE DORSAL 533 00:20:59,840 --> 00:21:00,120 ENDODERM. 534 00:21:00,120 --> 00:21:05,000 IT'S GRADED THE ENTIRE MESODERM 535 00:21:05,000 --> 00:21:06,640 EXPRESSING PATCH, ENOUGH TO 536 00:21:06,640 --> 00:21:09,200 INHIBIT ANY CARTILAGE ANYWHERE 537 00:21:09,200 --> 00:21:10,320 WITHIN THE TUBE. 538 00:21:10,320 --> 00:21:13,120 AS HEDGEHOG STARTS TO DECREASE 539 00:21:13,120 --> 00:21:15,240 EXPRESSION, REPRESENTED BY THE 540 00:21:15,240 --> 00:21:16,280 SMALLER DOMAIN, GRADIENT 541 00:21:16,280 --> 00:21:20,040 RETRACTS BECAUSE THERE'S LESS 542 00:21:20,040 --> 00:21:21,800 HEDGEHOG, LESS SIGNALING, NOW 543 00:21:21,800 --> 00:21:24,360 HAVE CELLS AT THE BOTTOM THAT NO 544 00:21:24,360 --> 00:21:26,600 LONGER SEE THE HEDGEHOG GRADIENT 545 00:21:26,600 --> 00:21:27,760 AND START MAKING CARTILAGE. 546 00:21:27,760 --> 00:21:29,920 IN A SERIES OF DOTS FOLLOWING 547 00:21:29,920 --> 00:21:31,040 THE TURING MECHANISM. 548 00:21:31,040 --> 00:21:34,640 WHAT HAPPENS THEN, AS THIS 549 00:21:34,640 --> 00:21:37,840 CONTINUES TO RETRACT, THIS 550 00:21:37,840 --> 00:21:42,200 RETRACTING GRADIENT PULL ALSO 551 00:21:42,200 --> 00:21:43,920 CARTILAGE INTO PERFECT RINGS. 552 00:21:43,920 --> 00:21:46,640 PREDICTIONS, IN THE CHICK OR 553 00:21:46,640 --> 00:21:49,400 MOUSE YOU WOULD EXPECT RINGS TO 554 00:21:49,400 --> 00:21:55,320 START AS SMALL DOMAINS ON THE 555 00:21:55,320 --> 00:21:58,240 VENTRAL SIDE, EXTENDING OVER 556 00:21:58,240 --> 00:21:58,920 TIME. 557 00:21:58,920 --> 00:22:01,400 TWO, SONIC HEDGEHOG GRADIENT 558 00:22:01,400 --> 00:22:02,400 RETRACTS OVER TIME. 559 00:22:02,400 --> 00:22:04,160 THREE, IF THIS IS WHAT'S GOING 560 00:22:04,160 --> 00:22:05,280 ON, ANYWHERE YOU HAVE HEDGEHOG 561 00:22:05,280 --> 00:22:09,000 SIGNALING YOU SHOULD NOT HAVE 562 00:22:09,000 --> 00:22:10,280 CARTILAGE AND VICE VERSA, THEY 563 00:22:10,280 --> 00:22:11,920 SHOULD BE COMPLEMENTARY DOMAINS. 564 00:22:11,920 --> 00:22:17,560 YOU CAN LOOK IN THE CHICK. 565 00:22:17,560 --> 00:22:19,720 ON THE VENTRAL SIDE YOU CAN 566 00:22:19,720 --> 00:22:22,400 CATCH IT IF YOU CHECK AT THE 567 00:22:22,400 --> 00:22:23,360 RIGHT TIME. 568 00:22:23,360 --> 00:22:24,560 GRADIENT RETRACTS OVER TIME, ONE 569 00:22:24,560 --> 00:22:26,160 EXTENDS AROUND THE FULL RING OR 570 00:22:26,160 --> 00:22:29,200 ALMOST THE FULL RING IN THIS IN 571 00:22:29,200 --> 00:22:31,560 SITU OVER TIME, LESS, LESS, 572 00:22:31,560 --> 00:22:31,880 SMALL. 573 00:22:31,880 --> 00:22:34,120 THIS IS LOOKING AT PATCH, 574 00:22:34,120 --> 00:22:34,920 READOUT FOR THE GRADIENT, 575 00:22:34,920 --> 00:22:37,640 HEDGEHOG ACTIVITY. 576 00:22:37,640 --> 00:22:39,200 AND INDEED ANY OF THESE STAGES 577 00:22:39,200 --> 00:22:42,680 IF YOU COMPARE HEDGEHOG ACTIVITY 578 00:22:42,680 --> 00:22:46,400 TO CHONDRAGENESIS, IN THIS CASE 579 00:22:46,400 --> 00:22:47,800 LOOKING AT HEDGEHOG REPORTER, 580 00:22:47,800 --> 00:22:50,880 THIS PINK IS PATCH, THIS IS SOX 581 00:22:50,880 --> 00:22:54,400 9, WE'RE LOOKING AT -- DON'T GET 582 00:22:54,400 --> 00:22:54,680 CONFUSED. 583 00:22:54,680 --> 00:22:55,920 PINK IS CARTILAGE, GREEN IS 584 00:22:55,920 --> 00:22:56,440 HEDGEHOG. 585 00:22:56,440 --> 00:22:58,640 YOU CAN SEE THERE'S A PERFECT 586 00:22:58,640 --> 00:22:59,400 RECIPROCAL RELATIONSHIP BETWEEN 587 00:22:59,400 --> 00:23:03,800 WHERE YOU HAVE HEDGEHOG AND 588 00:23:03,800 --> 00:23:06,360 WHERE YOU HAVE CARTILAGE. 589 00:23:06,360 --> 00:23:08,000 FINALLY WHEN WE PREDICT IF THIS 590 00:23:08,000 --> 00:23:10,080 IS WHAT'S HAPPENING, YOU CAN 591 00:23:10,080 --> 00:23:12,400 BLOCK HEDGEHOG SIGNALING, IF 592 00:23:12,400 --> 00:23:13,400 IT'S HEDGEHOG SIGNALING GIVING 593 00:23:13,400 --> 00:23:15,560 PERFECT RINGS RETRACTION OF THE 594 00:23:15,560 --> 00:23:18,280 GRADIENT, IF YOU BLOCK HEDGEHOG 595 00:23:18,280 --> 00:23:22,120 SIGNALING UNIFORMLY GET RIDDLE 596 00:23:22,120 --> 00:23:27,600 RID -- RID OF ALL, RETRACT FROM 597 00:23:27,600 --> 00:23:32,600 VENTRAL SIDE UP, SHOULD BE 598 00:23:32,600 --> 00:23:34,280 GETTING CHONDRAGENESIS 599 00:23:34,280 --> 00:23:34,600 EVERYWHERE. 600 00:23:34,600 --> 00:23:36,320 SOX9, YOU HAVE THE START OF THE 601 00:23:36,320 --> 00:23:38,160 CARTILAGE RINGS, THIS IS IN THE 602 00:23:38,160 --> 00:23:38,400 CONTROL. 603 00:23:38,400 --> 00:23:40,000 IF YOU BLOCK HEDGEHOG SIGNALING 604 00:23:40,000 --> 00:23:41,520 EVERYWHERE, YOU NOW GET THE 605 00:23:41,520 --> 00:23:45,080 STARTS OF RINGS IN THE VENTRAL 606 00:23:45,080 --> 00:23:46,680 SIDE, DORSAL SIDE, IN BETWEEN, 607 00:23:46,680 --> 00:23:48,640 CARTILAGE EVERYWHERE BECAUSE YOU 608 00:23:48,640 --> 00:23:50,640 DON'T HAVE INHIBITION OF 609 00:23:50,640 --> 00:23:50,920 HEDGEHOG. 610 00:23:50,920 --> 00:23:53,800 AND I ALLUDED TO THE IDEA THIS 611 00:23:53,800 --> 00:23:59,600 RECIPROCAL RELATIONSHIP BETWEEN 612 00:23:59,600 --> 00:24:00,480 CARTILAGE AND HEDGEHOG SIGNALING 613 00:24:00,480 --> 00:24:03,760 IN THE PROCESS OF GIVING YOU THE 614 00:24:03,760 --> 00:24:08,400 SYRINX, SUGGESTING PREEXISTING 615 00:24:08,400 --> 00:24:11,400 SYSTEM FOR FORMING CARTILAGE 616 00:24:11,400 --> 00:24:13,880 RINGS IN THE REPTILE. 617 00:24:13,880 --> 00:24:14,640 THIS IS ALLIGATOR. 618 00:24:14,640 --> 00:24:21,200 ONCE AGAIN YOU HAVE HEDGEHOG 619 00:24:21,200 --> 00:24:21,760 BEING RECIPROCAL OF 620 00:24:21,760 --> 00:24:24,440 CHONDRAGENESIS IN THE ALLIGATOR 621 00:24:24,440 --> 00:24:27,440 AS IN THE CHICK. 622 00:24:27,440 --> 00:24:29,600 FOCUSING ON CARTILAGE, I TRIED 623 00:24:29,600 --> 00:24:31,680 TO TELL YOU THAT YOU GET 624 00:24:31,680 --> 00:24:35,360 CARTILAGE RINGS IN THE TRACHEA 625 00:24:35,360 --> 00:24:39,240 AND BRONCHI THROUGH HAVING 626 00:24:39,240 --> 00:24:42,200 HEDGEHOG RETRACTION, OVER TIME 627 00:24:42,200 --> 00:24:44,640 MORE CAPACITY FOR 628 00:24:44,640 --> 00:24:45,920 CHONDRAGENESIS, DRAWING THIS 629 00:24:45,920 --> 00:24:48,720 INITIAL LINEAR TURING PATTERN 630 00:24:48,720 --> 00:24:50,280 INTO PERFECTLY PARALLEL RINGS. 631 00:24:50,280 --> 00:24:53,360 BY HAVING THIS PROCESS TAKE 632 00:24:53,360 --> 00:24:54,560 PLACE EARLIER, WHERE THE SYRINX 633 00:24:54,560 --> 00:24:57,400 IS GOING TO FORM, YOU GET RID OF 634 00:24:57,400 --> 00:25:02,440 THE INTERFERENCE PATTERNS FROM 635 00:25:02,440 --> 00:25:03,400 COLLIDING TURING MECHANISMS, 636 00:25:03,400 --> 00:25:09,160 FORMING PERFECT CARTILAGE FOR 637 00:25:09,160 --> 00:25:11,160 SYRINX BEFORE FORMING BRONCHIAL 638 00:25:11,160 --> 00:25:12,840 AND TRACHEAL RINGS. 639 00:25:12,840 --> 00:25:18,400 NOW WE HAVE A VOICE BOX, THINK 640 00:25:18,400 --> 00:25:19,880 ABOUT VIBRATORY TISSUE. 641 00:25:19,880 --> 00:25:22,080 HOMOLOGY CONTEXT, THE SYRINX AND 642 00:25:22,080 --> 00:25:25,520 LARYNX ARE ANALOGOUS, USED TO 643 00:25:25,520 --> 00:25:25,840 MAKE SOUNDS. 644 00:25:25,840 --> 00:25:29,480 BUT TO WHAT EXTENT ARE THEY THE 645 00:25:29,480 --> 00:25:30,040 SAME ANIMAL? 646 00:25:30,040 --> 00:25:31,680 HUXLEY REFERRED TO THEM AS BEING 647 00:25:31,680 --> 00:25:33,000 THE SAME. 648 00:25:33,000 --> 00:25:35,000 BIRDS POSSESS A LARYNX IN THE 649 00:25:35,000 --> 00:25:37,600 ORDINARY POSITION, USE ANOTHER 650 00:25:37,600 --> 00:25:40,440 APPARATUS, HE CALLED LOWER 651 00:25:40,440 --> 00:25:41,200 LARYNX OR SYRINX, REFERRING TO 652 00:25:41,200 --> 00:25:43,720 THE SYRINX AS A SECOND LARYNX 653 00:25:43,720 --> 00:25:44,920 FURTHER DOWN SUGGESTING SOME 654 00:25:44,920 --> 00:25:48,680 SORT OF -- IMPLYING HOMOLOGY. 655 00:25:48,680 --> 00:25:51,600 HOW HOMOLOGOUS ARE THEY? 656 00:25:51,600 --> 00:25:56,000 A GRADUATE STUDENT PICKED THIS 657 00:25:56,000 --> 00:25:56,400 UP. 658 00:25:56,400 --> 00:26:00,800 HE LOOKED AT THE TISSUE LEVEL, 659 00:26:00,800 --> 00:26:01,200 SIMILAR TISSUES. 660 00:26:01,200 --> 00:26:02,720 CERTAINLY IN TERMS OF 661 00:26:02,720 --> 00:26:04,400 EXTRACELLULAR MATRIX, THEY ARE. 662 00:26:04,400 --> 00:26:10,280 SYRINX EXPRESSES A VARIETY OF 663 00:26:10,280 --> 00:26:11,800 EXTRACELLULAR MATRIX GIVING 664 00:26:11,800 --> 00:26:16,000 VIBRATORY PROCESS, LARYNX 665 00:26:16,000 --> 00:26:16,760 EXPRESSES SAME MOLECULES, 666 00:26:16,760 --> 00:26:19,000 HYALURONIC ACID, A NUMBER OF 667 00:26:19,000 --> 00:26:19,480 OTHERS. 668 00:26:19,480 --> 00:26:21,560 THAT RAISES AT LEAST THREE 669 00:26:21,560 --> 00:26:25,720 POSSIBILITIES HOW OF SYRINX AND 670 00:26:25,720 --> 00:26:27,600 LARYNX HAVE SIMILAR TISSUE 671 00:26:27,600 --> 00:26:28,400 PROBLEMS. 672 00:26:28,400 --> 00:26:30,200 CONVERGENCE, THEY HAVE TO 673 00:26:30,200 --> 00:26:33,000 VIBRATE AND MAKE SOUND, 674 00:26:33,000 --> 00:26:33,600 CONSTRAINS WITH MECHANICAL 675 00:26:33,600 --> 00:26:38,160 PROPERTIES, MAYBE THESE ARE THE 676 00:26:38,160 --> 00:26:38,920 OPTIMAL EXTRACELLULAR MATRIX 677 00:26:38,920 --> 00:26:41,560 PROTEINS, AND INDEPENDENTLY BUT 678 00:26:41,560 --> 00:26:42,840 THROUGH PARALLEL EVOLUTION 679 00:26:42,840 --> 00:26:49,800 EVOLVE IN THE SYRINX AND LARYNX. 680 00:26:49,800 --> 00:26:53,160 OR, BOTTOM, THEY COULD BE 681 00:26:53,160 --> 00:26:54,360 HOMOLOGOUS, MAYBE PROGENITOR 682 00:26:54,360 --> 00:26:57,600 CELLS THAT MAKE THE VOCAL FOLDS 683 00:26:57,600 --> 00:26:59,800 IN MAMMAL AND AVIAN SYSTEM ARE 684 00:26:59,800 --> 00:27:00,600 THE SAME TISSUE. 685 00:27:00,600 --> 00:27:04,440 A LOT OF MIGRATORY CELLS IN THE 686 00:27:04,440 --> 00:27:07,600 EMBRYO, MAYBE THE CELLS MIGRATE 687 00:27:07,600 --> 00:27:15,440 TO THE SYRINX IN A BIRD, REALLY 688 00:27:15,440 --> 00:27:17,000 HOMOLOGOUS OR PROCESS HOMOLOGY 689 00:27:17,000 --> 00:27:18,200 OR DEEP HOMOLOGY, REFERRING TO A 690 00:27:18,200 --> 00:27:24,560 CASE WHERE YOU HAVE STRUCTURES 691 00:27:24,560 --> 00:27:26,200 THAT EVOLVE INDEPENDENTLY, YOU 692 00:27:26,200 --> 00:27:31,800 COULD IMAGINE GENE REGULATORY 693 00:27:31,800 --> 00:27:33,040 NETWORK STOLEN BY EVOLUTION, 694 00:27:33,040 --> 00:27:34,400 CO-OPTED TO MAKE A SYRINX 695 00:27:34,400 --> 00:27:36,200 BUILDING IT IN A DIFFERENT PLACE 696 00:27:36,200 --> 00:27:37,840 AND DIFFERENT WAY. 697 00:27:37,840 --> 00:27:42,000 FIRST QUESTION IS ARE THEY THE 698 00:27:42,000 --> 00:27:43,040 SAME -- REALLY HOMOLOGOUS, ARE 699 00:27:43,040 --> 00:27:44,760 TISSUES THE SAME THING? 700 00:27:44,760 --> 00:27:53,200 WE CAN ELIMINATE THAT QUICKLY. 701 00:27:53,200 --> 00:27:55,720 OTHER INVESTIGATORS, TIBLER ET 702 00:27:55,720 --> 00:27:58,400 AL. IN WALLINGFORD'S LABORATORY, 703 00:27:58,400 --> 00:28:05,800 MAP INCOME THE MOUSE, VOCAL 704 00:28:05,800 --> 00:28:07,760 CORDS OF NEURAL CREST ORIGIN, A 705 00:28:07,760 --> 00:28:10,800 CELL TYPE THAT MIGRATES AROUND 706 00:28:10,800 --> 00:28:12,560 AND USES MIGRATORY CELLS 707 00:28:12,560 --> 00:28:16,640 ORIGINATING IN THE ECTODERM, THE 708 00:28:16,640 --> 00:28:18,600 JUNCTION OF THE NEURAL CREST. 709 00:28:18,600 --> 00:28:20,400 THESE ARE MIGRATORY CELLS. 710 00:28:20,400 --> 00:28:22,760 IF NEURAL CREST WAS CELLS MADE 711 00:28:22,760 --> 00:28:25,640 UP OF THE SYRINX VOCAL CORDS, 712 00:28:25,640 --> 00:28:29,200 THAT MODEL MIGHT HOLD. 713 00:28:29,200 --> 00:28:30,960 SO WE DID TRANSPLANT 714 00:28:30,960 --> 00:28:31,600 EXPERIMENTS, NEURAL CREST COMES 715 00:28:31,600 --> 00:28:34,280 FROM THE TO BE OF THE NEURAL 716 00:28:34,280 --> 00:28:40,920 TUBE, CUT OUT THE NEURAL TUBE 717 00:28:40,920 --> 00:28:43,520 FROM WILDTYPE CHICKEN, GRAFT GFP 718 00:28:43,520 --> 00:28:47,160 NEURAL TUBE, AND IN THIS 719 00:28:47,160 --> 00:28:50,640 CONFIGURATION, A REAL EMBRYO, 720 00:28:50,640 --> 00:28:52,800 THE CELLS WILL INTEGRATE INTO 721 00:28:52,800 --> 00:28:55,760 THE HOST, PLAY THE ROLES THEY 722 00:28:55,760 --> 00:28:58,280 WOULD HAVE PLAYED IN THE NORMAL 723 00:28:58,280 --> 00:28:58,600 SETTING. 724 00:28:58,600 --> 00:29:01,160 YOU CAN ASK WHAT TISSUES DOES 725 00:29:01,160 --> 00:29:02,640 THAT GIVE RISE TO? 726 00:29:02,640 --> 00:29:04,600 THERE'S PLENTY OF CREST ARRANGED 727 00:29:04,600 --> 00:29:05,920 THE NEURAL SYRINX, ALL THIS 728 00:29:05,920 --> 00:29:09,520 TISSUE SHOWN IN PURPLE IS NEURAL 729 00:29:09,520 --> 00:29:11,440 CREST. 730 00:29:11,440 --> 00:29:14,120 IT'S ALL INNERVATION. 731 00:29:14,120 --> 00:29:15,440 THE SYMPATHETIC NERVOUS SYSTEM, 732 00:29:15,440 --> 00:29:16,520 CRANIAL NERVES AND SO ON. 733 00:29:16,520 --> 00:29:19,120 WHAT YOU DON'T SEE IS PURPLE IN 734 00:29:19,120 --> 00:29:21,000 THE SYRINX OR TRACHEA OR BRONCHI 735 00:29:21,000 --> 00:29:22,400 FOR THAT MATTER. 736 00:29:22,400 --> 00:29:26,120 SYRINX ITSELF IS NOT MADE OF 737 00:29:26,120 --> 00:29:26,880 NEURAL CREST. 738 00:29:26,880 --> 00:29:29,080 ANOTHER TRANSPLANT FROM LATERAL 739 00:29:29,080 --> 00:29:30,000 PLATE MESODERM. 740 00:29:30,000 --> 00:29:31,640 THEY COME FROM DIFFERENT 741 00:29:31,640 --> 00:29:31,880 TISSUES. 742 00:29:31,880 --> 00:29:34,320 THEREFORE THEY ARE NOT 743 00:29:34,320 --> 00:29:34,800 HOMOLOGOUS. 744 00:29:34,800 --> 00:29:36,200 WHAT ABOUT PROCESS HOMOLOGY? 745 00:29:36,200 --> 00:29:37,920 ARE THE SAME REGULATORY NETWORKS 746 00:29:37,920 --> 00:29:40,120 USED TO MAKE BOTH SYRINX AND 747 00:29:40,120 --> 00:29:40,360 LARYNX? 748 00:29:40,360 --> 00:29:45,680 TO KNOW THAT YOU HAVE TO KNOW 749 00:29:45,680 --> 00:29:48,680 WHAT SORT OF REGULATORY 750 00:29:48,680 --> 00:29:49,600 CIRCUMSTANCES THERE ARE MAKING 751 00:29:49,600 --> 00:29:50,360 SYRINX OR LARYNX. 752 00:29:50,360 --> 00:29:55,120 THERE'S BEEN A LOT OF WORK ON 753 00:29:55,120 --> 00:29:56,080 THE MAMMALIAN AIRWAY AND 754 00:29:56,080 --> 00:29:58,320 VOCALIZATION OF BIRDS AT THE 755 00:29:58,320 --> 00:29:59,800 LEVEL OF NEURAL CIRCUITRY, 756 00:29:59,800 --> 00:30:01,200 REALLY NOTHING WAS KNOWN ABOUT 757 00:30:01,200 --> 00:30:02,080 GENE REGULATORY NETWORKS THAT 758 00:30:02,080 --> 00:30:03,840 GIVE YOU A VOCAL CORD. 759 00:30:03,840 --> 00:30:07,680 SO TO GET A HANDLE ON THAT 760 00:30:07,680 --> 00:30:12,240 CHARLIE DID SINGLE CELL RNAseq 761 00:30:12,240 --> 00:30:15,400 EXPERIMENTS, DISASSOCIATE CELLS 762 00:30:15,400 --> 00:30:17,760 AT STAGES, SINGLE CELL 763 00:30:17,760 --> 00:30:19,920 SEQUENCING, CLUSTERED ON GENE 764 00:30:19,920 --> 00:30:21,880 EXPRESSION. 765 00:30:21,880 --> 00:30:24,080 EACH CLUSTER, EACH COLOR, 766 00:30:24,080 --> 00:30:26,360 LABELING CLUSTERS THAT HAVE 767 00:30:26,360 --> 00:30:29,600 DIFFERENT SORT OF 768 00:30:29,600 --> 00:30:30,520 TRANSCRIPTIONAL PROFILES, YOU 769 00:30:30,520 --> 00:30:31,840 CAN RECOGNIZE, I'VE LABELED WHAT 770 00:30:31,840 --> 00:30:36,760 THE CLUSTERS WOULD RELATE TO. 771 00:30:36,760 --> 00:30:37,840 FOR EXAMPLE, PRE-CARTILAGE 772 00:30:37,840 --> 00:30:38,880 CELLS, CARTILAGE CELLS, 773 00:30:38,880 --> 00:30:40,480 ENDODERM, SO ON, BASED ON 774 00:30:40,480 --> 00:30:40,840 MARKERS. 775 00:30:40,840 --> 00:30:43,200 YOU CAN TELL WHICH ARE CARTILAGE 776 00:30:43,200 --> 00:30:47,080 BECAUSE THEY EXPRESS VERY 777 00:30:47,080 --> 00:30:48,680 SPECIFICALLY CARTILAGE-SPECIFIC 778 00:30:48,680 --> 00:30:51,640 GENES LIKE COLLAGEN 2A 1 AND 9A 779 00:30:51,640 --> 00:30:51,840 1. 780 00:30:51,840 --> 00:30:54,680 WHAT WE'RE LOOKING FOR ARE 781 00:30:54,680 --> 00:30:57,360 THE -- IS THE CLUSTER THAT MIGHT 782 00:30:57,360 --> 00:30:58,880 BE RELEVANT FOR VOCAL CORDS. 783 00:30:58,880 --> 00:31:00,960 AND THE ONE THAT POPPED OUT IS 784 00:31:00,960 --> 00:31:03,200 THIS ONE HERE. 785 00:31:03,200 --> 00:31:09,000 IT'S SHOWN ON THIS DIAGRAM RA+, 786 00:31:09,000 --> 00:31:11,600 IF YOU LOOK AT EXTRACELLULAR 787 00:31:11,600 --> 00:31:14,320 MATRIX FOR GENE EXPRESSION OF 788 00:31:14,320 --> 00:31:15,560 EXTRACELLULAR MATRIX PROTEINS, 789 00:31:15,560 --> 00:31:17,000 THEY ARE SPECIFICALLY FOUND IN 790 00:31:17,000 --> 00:31:19,800 THE SYRINX ITSELF. 791 00:31:19,800 --> 00:31:21,120 WITHIN THE VOCAL TISSUE. 792 00:31:21,120 --> 00:31:24,000 THOSE ARE VERY HIGHLY EXPRESSED 793 00:31:24,000 --> 00:31:26,160 TOGETHER, CLUSTER 10. 794 00:31:26,160 --> 00:31:27,160 INDEPENDENTLY EXPRESSED IN OTHER 795 00:31:27,160 --> 00:31:28,360 CLUSTERS BUT THE ONLY PLACE YOU 796 00:31:28,360 --> 00:31:31,200 HAVE BOTH AS WELL AS OTHER 797 00:31:31,200 --> 00:31:32,720 EXTRACELLULAR MATRIX PROTEINS 798 00:31:32,720 --> 00:31:34,400 ARE CLUSTER 10. 799 00:31:34,400 --> 00:31:36,120 STRIKINGLY CLUSTER 10 IS 800 00:31:36,120 --> 00:31:41,920 INTRIGUING, EXPRESSES A NUMBER 801 00:31:41,920 --> 00:31:44,200 OF GENES, SYNTHESIS PATHWAY, 802 00:31:44,200 --> 00:31:45,840 RETINOIC ACID IN GENES 803 00:31:45,840 --> 00:31:51,560 UPREGULATED BY RETINOIC ACID, 804 00:31:51,560 --> 00:31:52,960 CONVERSELY NOTICEABLE 805 00:31:52,960 --> 00:31:58,000 DOWNREGULATION OF RNA RETINOIC'S 806 00:31:58,000 --> 00:32:06,080 A IT ANTAGONIST SUCH AS CRABP-1. 807 00:32:06,080 --> 00:32:07,840 THE SYRINX PRIMORDIAN HAS 808 00:32:07,840 --> 00:32:12,080 SIGNIFICANT AMOUNT OF RETINOIC 809 00:32:12,080 --> 00:32:13,200 SIGNALING. 810 00:32:13,200 --> 00:32:16,800 LOOKING AT LOCI, SHOWING THE 811 00:32:16,800 --> 00:32:20,000 CASE BY VERIFYING THE CLUSTERING 812 00:32:20,000 --> 00:32:22,240 RESULTS IN VIVO, HERE'S 813 00:32:22,240 --> 00:32:25,800 EXPRESSION OF GENE, ONE OF THE 814 00:32:25,800 --> 00:32:27,320 GENES MARKED IN RETINOIC ACID 815 00:32:27,320 --> 00:32:34,680 ACTIVITY AT THE SYRINX, TRACHEA 816 00:32:34,680 --> 00:32:36,400 UP HERE, SYRINX HERE, BETWEEN 817 00:32:36,400 --> 00:32:40,000 THE TWO RETINOIC ACID ACTIVITY, 818 00:32:40,000 --> 00:32:41,360 DEGRADATION ABOVE AND BELOW, 819 00:32:41,360 --> 00:32:43,160 DECREASE AT THE SYRINX. 820 00:32:43,160 --> 00:32:49,400 THAT'S WHERE YOU FIND VARIOUS 821 00:32:49,400 --> 00:32:50,960 EXTRACELLULAR MATRIX PROTEINS 822 00:32:50,960 --> 00:32:57,200 SUCH AS ALCIAN BLUE STAINING, 823 00:32:57,200 --> 00:32:59,680 STAINS FOR ACIDIC GLYCANS. 824 00:32:59,680 --> 00:33:01,680 TO SHOW THIS ANOTHER WAY, YOU 825 00:33:01,680 --> 00:33:04,600 HAVE -- YOU CAN SHOW IF YOU PLOT 826 00:33:04,600 --> 00:33:06,480 BACK TO THE CLUSTERS, CELLS THAT 827 00:33:06,480 --> 00:33:08,840 ARE EXPRESSING, FOR EXAMPLE, 828 00:33:08,840 --> 00:33:11,920 CARTILAGE MARKER, COLLAGEN 829 00:33:11,920 --> 00:33:14,360 MARKER, RETINOIC ACID, TO WHAT 830 00:33:14,360 --> 00:33:18,960 EXTENT DO THEY SUPPRESS AN 831 00:33:18,960 --> 00:33:21,680 EXTRACELLULAR MATRIX PROTEIN, 832 00:33:21,680 --> 00:33:31,200 LUMICAN IS EXPRESSED AS IS 833 00:33:31,200 --> 00:33:33,480 FIBRONECTIN AS IS HYALURONIC 834 00:33:33,480 --> 00:33:33,680 ACID. 835 00:33:33,680 --> 00:33:36,400 RETINOIC ACID IS THE SAME PLACE 836 00:33:36,400 --> 00:33:38,200 AS EXTRACELLULAR PROTEINS. 837 00:33:38,200 --> 00:33:44,280 ANOTHER GENE THAT POPPED OUT, 838 00:33:44,280 --> 00:33:44,720 SOX9. 839 00:33:44,720 --> 00:33:46,280 SOX9 IS EXPRESSED IN CARTILAGE 840 00:33:46,280 --> 00:33:46,600 DEVELOPMENT. 841 00:33:46,600 --> 00:33:49,080 YOU CAN SEE IT IN CARTILAGE 842 00:33:49,080 --> 00:33:50,520 RINGS. 843 00:33:50,520 --> 00:33:57,120 IT'S NOT A CHONDROGENIC -- IT'S 844 00:33:57,120 --> 00:34:00,520 A TRANSCRIPTION FACTOR, SOX9 IN 845 00:34:00,520 --> 00:34:03,600 VALVES OF THE HEART, FIRST PLACE 846 00:34:03,600 --> 00:34:09,120 IT WAS WELL CHARACTERIZED IN THE 847 00:34:09,120 --> 00:34:11,080 TESTES, KEY GENE FOR 848 00:34:11,080 --> 00:34:13,200 ESTABLISHING PHENOTYPE. 849 00:34:13,200 --> 00:34:16,280 IN ADDITION TO THESE EXPRESSION 850 00:34:16,280 --> 00:34:20,520 OF CARTILAGE RINGS, HIGH 851 00:34:20,520 --> 00:34:22,960 EXPRESSION OF SOX9 ADJACENT TO 852 00:34:22,960 --> 00:34:26,000 THE PLACE WITH HYALURONIC ACID. 853 00:34:26,000 --> 00:34:27,840 SO, EXTRACELLULAR MATRIX 854 00:34:27,840 --> 00:34:28,680 PROTEINS, TRANSCRIPTIONAL 855 00:34:28,680 --> 00:34:29,440 REGULATOR, SIGNALING PATHWAY, 856 00:34:29,440 --> 00:34:31,160 ARE THEY ALL RELATED TO EACH 857 00:34:31,160 --> 00:34:31,400 OTHER? 858 00:34:31,400 --> 00:34:34,880 FIRST OF ALL WE CAN SHOW 859 00:34:34,880 --> 00:34:38,480 RETINOIC ACID ACTS UPSTREAM OF 860 00:34:38,480 --> 00:34:41,000 SOX9 AND EXTRACELLULAR MATRIX, 861 00:34:41,000 --> 00:34:48,000 CONTROL SYRINX HERE IS SHOWING 862 00:34:48,000 --> 00:34:51,840 SOX9 IN GENE, HABP IS BINDING 863 00:34:51,840 --> 00:34:53,720 PROTEIN, A PROBE, LABELED 864 00:34:53,720 --> 00:34:57,240 BINDING PROTEIN IN VITRO THAT 865 00:34:57,240 --> 00:35:01,400 USES A PROBE TO DETECT 866 00:35:01,400 --> 00:35:05,840 HYALURONIC ACID IN VIVO. 867 00:35:05,840 --> 00:35:09,800 IF YOU TWEAK PARALLEL CULTURE 868 00:35:09,800 --> 00:35:25,160 SYRINX, WITH RETINOIC'S 869 00:35:25,160 --> 00:35:29,880 RETINOIC ACID INHIBITOR. 870 00:35:29,880 --> 00:35:30,960 UPREGULATE RETINOIC ACID, GET 871 00:35:30,960 --> 00:35:36,640 HYALURONIC ACID, DO NOT GET 872 00:35:36,640 --> 00:35:37,200 SOX9. 873 00:35:37,200 --> 00:35:44,640 RETINOIC ACID IS NECESSARY FOR 874 00:35:44,640 --> 00:35:46,360 SOX9 AND EXTRACELLULAR MATRIX, 875 00:35:46,360 --> 00:35:49,240 SUFFICIENT -- NOT FOR THE 876 00:35:49,240 --> 00:35:50,640 EXPRESSION OF SOX9. 877 00:35:50,640 --> 00:35:52,520 YOU CAN QUANTIFY THIS 878 00:35:52,520 --> 00:35:53,920 DEPENDENCE, THIS IS WITH 879 00:35:53,920 --> 00:35:55,360 RETINOIC ACID INHIBITOR, OR 880 00:35:55,360 --> 00:35:57,720 CONTROL, SHOWING YOU HAVE 881 00:35:57,720 --> 00:36:01,000 INCREASE IN BOTH SOX9, DECREASE 882 00:36:01,000 --> 00:36:02,200 IN SOX9 SIGNALING AND DECREASE 883 00:36:02,200 --> 00:36:04,880 IN HYALURONIC ACID BINDING 884 00:36:04,880 --> 00:36:07,000 PROTEIN SIGNALING WHEN YOU TREAT 885 00:36:07,000 --> 00:36:08,720 WITH INHIBITOR OF RETINOIC ACID. 886 00:36:08,720 --> 00:36:11,200 SO, WE HAVE AT LEAST A START OF 887 00:36:11,200 --> 00:36:12,600 A REGULATION, WHERE RETINOIC 888 00:36:12,600 --> 00:36:15,000 ACID IS UPSTREAM OF SOX9 AND 889 00:36:15,000 --> 00:36:16,600 EXTRACELLULAR MATRIX, WHAT ABOUT 890 00:36:16,600 --> 00:36:16,920 SOX9? 891 00:36:16,920 --> 00:36:19,000 DOES IT PLAY A ROLE IN 892 00:36:19,000 --> 00:36:19,920 REGULATING EXTRACELLULAR MATRIX? 893 00:36:19,920 --> 00:36:22,080 WE LOOKED AT THAT AS WELL. 894 00:36:22,080 --> 00:36:23,600 IN THIS CASE START WITH UPPER 895 00:36:23,600 --> 00:36:26,400 PANEL, LOOK AT THE TRACHEA. 896 00:36:26,400 --> 00:36:29,800 IN THE TRACHEA, WHICH NORMALLY 897 00:36:29,800 --> 00:36:31,640 DOES NOT EXPRESS SOX9 HYALURONIC 898 00:36:31,640 --> 00:36:34,000 ACID BINDING PROTEIN, IF YOU 899 00:36:34,000 --> 00:36:36,080 COME IN WITH RETROVIRAL VECTOR 900 00:36:36,080 --> 00:36:39,360 THAT CARRIES SOX9 IN RESPONSE TO 901 00:36:39,360 --> 00:36:45,480 THAT ECTOPIC SOX89 YOU HAVE 902 00:36:45,480 --> 00:36:46,840 HYALURONIC ACID QUANTIFIED 903 00:36:46,840 --> 00:36:53,320 WITHOUT RETINOIC ACID AND -- 904 00:36:53,320 --> 00:36:54,400 SORRY, WITH AND WITHOUT SOX9. 905 00:36:54,400 --> 00:36:58,080 IF YOU GO TO THE SYRINX AND ADD 906 00:36:58,080 --> 00:37:01,840 TO THE SYRINX VOCAL FOLDS, IN 907 00:37:01,840 --> 00:37:04,200 THIS CASE NEGATIVE SOX9, VOCAL 908 00:37:04,200 --> 00:37:04,920 FOLDS NORMALLY HAVE HYALURONIC 909 00:37:04,920 --> 00:37:06,800 ACID. 910 00:37:06,800 --> 00:37:11,560 IF YOU COME IN WITH DOMINANT 911 00:37:11,560 --> 00:37:14,160 NEGATIVE SOX9, SYRINX CEASES TO 912 00:37:14,160 --> 00:37:14,680 MAKE HYALURONIC ACID. 913 00:37:14,680 --> 00:37:16,560 SO HYALURONIC ACID IS DOWNSTREAM 914 00:37:16,560 --> 00:37:19,280 OF SOX9. 915 00:37:19,280 --> 00:37:21,840 SO ARE OTHER EXTRACELLULAR 916 00:37:21,840 --> 00:37:27,200 MATRIX PROTEINS, LOW LEVELS OF 917 00:37:27,200 --> 00:37:30,600 ELASTIN AND VERSICAN, PUT IN 918 00:37:30,600 --> 00:37:35,200 SOX9, BOTH ARE INDUCED. 919 00:37:35,200 --> 00:37:37,600 YOU HAVE THIS PATHWAY, AND THAT 920 00:37:37,600 --> 00:37:39,760 MAKES GOOD SENSE BECAUSE FROM AN 921 00:37:39,760 --> 00:37:44,400 EVOLUTIONARY STANDPOINT IF YOU 922 00:37:44,400 --> 00:37:46,040 WANT TO EVOLVE TISSUE THAT HAS 923 00:37:46,040 --> 00:37:47,160 PROPERTIES OF VOCAL FOLDS, 924 00:37:47,160 --> 00:37:50,200 INSTEAD OF COMING IN ONE AT A 925 00:37:50,200 --> 00:37:51,560 TIME BY SELECTING INDEPENDENTLY 926 00:37:51,560 --> 00:37:53,800 WHOLE SERIES OF DIFFERENT GENES 927 00:37:53,800 --> 00:37:56,040 TO BUILD DIFFERENT EXTRACELLULAR 928 00:37:56,040 --> 00:37:57,320 MATRIX PROTEINS, YOU CAN COME IN 929 00:37:57,320 --> 00:37:59,080 WITH ONE OR TWO REGULATORY 930 00:37:59,080 --> 00:38:00,600 MOLECULES, IF YOU CAN ACTIVATE 931 00:38:00,600 --> 00:38:03,560 THEM IN AN ECTOPIC PLACE, IF THE 932 00:38:03,560 --> 00:38:05,320 CELLS ARE COMPETENT TO RECEIVE 933 00:38:05,320 --> 00:38:08,520 THE SIGNAL, YOU CAN TURN ON THE 934 00:38:08,520 --> 00:38:10,720 WHOLE SET OF DOWNSTREAM CELLULAR 935 00:38:10,720 --> 00:38:14,800 PROTEINS IMPORTANT FOR GIVING 936 00:38:14,800 --> 00:38:16,080 TISSUE INTEGRITY. 937 00:38:16,080 --> 00:38:18,360 SO, THAT IMPLIES IF THAT'S TRUE 938 00:38:18,360 --> 00:38:22,320 THAT THIS SORT OF INTERACTION IS 939 00:38:22,320 --> 00:38:29,560 ALSO PRESENT IN THE MAMMALIAN 940 00:38:29,560 --> 00:38:30,440 LARYNX, ANCESTRAL ALLIGATOR, AS 941 00:38:30,440 --> 00:38:33,880 AVIAN SYRINX. 942 00:38:33,880 --> 00:38:35,480 SO THAT'S TO SAY ELIMINATED 943 00:38:35,480 --> 00:38:40,200 HOMOLOGY BUT STILL HAVEN'T 944 00:38:40,200 --> 00:38:43,000 DECIDED BETWEEN DEEP HOMOLOGY OR 945 00:38:43,000 --> 00:38:43,800 PROCESS HOMOLOGY VERSUS 946 00:38:43,800 --> 00:38:44,160 CONVERGENCE. 947 00:38:44,160 --> 00:38:48,400 SO TO DO THAT WE HAVE TO LOOK AT 948 00:38:48,400 --> 00:38:49,840 MAMMALS AND CROCODILES. 949 00:38:49,840 --> 00:38:53,000 FIRST WE'LL LOOK AT ALLIGATORS 950 00:38:53,000 --> 00:38:54,800 TO SEE IF THEY HAVE THE SAME 951 00:38:54,800 --> 00:38:58,080 GENES. 952 00:38:58,080 --> 00:39:00,240 WE DON'T HAVE FUNCTIONAL DATA, 953 00:39:00,240 --> 00:39:01,600 NOT MUCH, BUT WE HAVE SOME 954 00:39:01,600 --> 00:39:02,680 EXPRESSION DATA. 955 00:39:02,680 --> 00:39:08,080 SO YOU CAN SEE IN THE 956 00:39:08,080 --> 00:39:11,600 ALLIGATORS, ALLIGATOR AS IN THE 957 00:39:11,600 --> 00:39:13,440 CHICK, VERY SPECIFICALLY 958 00:39:13,440 --> 00:39:17,560 EXPRESSES SOX9 AND RETINOIC 959 00:39:17,560 --> 00:39:19,600 ACID SIGNALING AT VOCAL FOLDS, 960 00:39:19,600 --> 00:39:22,360 NOT IN THE TRACHEA OR SYRINX, 961 00:39:22,360 --> 00:39:24,600 THESE ARE IN THE LARYNX. 962 00:39:24,600 --> 00:39:25,600 LARYNGEAL VOCAL FOLDS, THE ONES 963 00:39:25,600 --> 00:39:28,880 I'M TALKING TO YOU WITH, DURING 964 00:39:28,880 --> 00:39:32,360 THEIR ONTOGENY EXPRESS THE SAME 965 00:39:32,360 --> 00:39:34,000 REGULATORS AS SYRINX DOES IN ITS 966 00:39:34,000 --> 00:39:34,280 ONTOGENY. 967 00:39:34,280 --> 00:39:35,760 YOU CAN SEE THE SAME SORT OF 968 00:39:35,760 --> 00:39:38,360 THING IN THE MOUSE, HERE SHOWING 969 00:39:38,360 --> 00:39:50,520 YOU THE CHICK SYRINX, AGAIN SOX 970 00:39:50,520 --> 00:39:50,800 9. 971 00:39:50,800 --> 00:39:56,400 YOU HAVE THE SAME EXPRESSION OF 972 00:39:56,400 --> 00:40:01,840 MATRIX PROTEIN, SAME REGULATORS 973 00:40:01,840 --> 00:40:04,280 ON RETINOIC ACID. 974 00:40:04,280 --> 00:40:05,800 ONE FUNCTIONAL ANALYSIS, DOES 975 00:40:05,800 --> 00:40:07,600 SOX9 HAVE THE SAME CAPABILITY 976 00:40:07,600 --> 00:40:10,920 TURNING ON IN THE MAMMAL AS 977 00:40:10,920 --> 00:40:12,600 BIRD? 978 00:40:12,600 --> 00:40:16,320 EXPRESSING IN TRACHEAL 979 00:40:16,320 --> 00:40:17,240 MESENCHYME SOX9 TURNS ON 980 00:40:17,240 --> 00:40:19,160 HYALURONIC ACID, YOU CAN SEE IT 981 00:40:19,160 --> 00:40:21,920 QUANTIFIED HERE. 982 00:40:21,920 --> 00:40:23,600 AGAIN HERE. 983 00:40:23,600 --> 00:40:38,240 NOT JUST HYALURONIC ACID BUT 984 00:40:38,240 --> 00:40:38,520 VERSICAN. 985 00:40:38,520 --> 00:40:39,160 MAMMALS AND CROCODILES EVOLVED 986 00:40:39,160 --> 00:40:40,160 TO TAKE PLACE IN THE FORMATION 987 00:40:40,160 --> 00:40:43,760 OF THE VOCAL FOLDS OF THE 988 00:40:43,760 --> 00:40:44,480 LARYNX. 989 00:40:44,480 --> 00:40:46,000 IN BIRDS, AS NEW VOCAL ORGAN WAS 990 00:40:46,000 --> 00:40:48,640 FORMED, IT'S FORMED OUT OF 991 00:40:48,640 --> 00:40:50,080 TOTALLY DIFFERENT TISSUE, WE 992 00:40:50,080 --> 00:40:53,000 THINK IT CO-OPTED THIS 993 00:40:53,000 --> 00:40:57,000 REGULATORY PATHWAY, AND BY 994 00:40:57,000 --> 00:40:58,760 CO-OPTING UPPER END, GOT THE 995 00:40:58,760 --> 00:41:00,200 DOWNSTREAM PARTS COMING FOR SHOW 996 00:41:00,200 --> 00:41:00,960 WITHOUT HAVING TO INDEPENDENTLY 997 00:41:00,960 --> 00:41:02,920 SELECT FOR EACH OF THE MOLECULES 998 00:41:02,920 --> 00:41:05,520 AGAIN THAT HAVE BEEN OPTIMIZED 999 00:41:05,520 --> 00:41:06,400 FOR VOCAL TISSUE. 1000 00:41:06,400 --> 00:41:08,880 NOW, I TOLD YOU WE DON'T KNOW 1001 00:41:08,880 --> 00:41:11,200 MUCH, BEFORE WE STARTED WORKING 1002 00:41:11,200 --> 00:41:18,320 ON THIS, NOTHING WAS KNOWN ABOUT 1003 00:41:18,320 --> 00:41:19,200 REGULATION OF VIBRATORY 1004 00:41:19,200 --> 00:41:20,640 MESENCHYME BUT ONE MORE PARALLEL 1005 00:41:20,640 --> 00:41:24,880 TO DRAW FOR YOU, NOT OF THE 1006 00:41:24,880 --> 00:41:26,800 VOCAL FOLD BUT EPITHELIUM, THAT 1007 00:41:26,800 --> 00:41:29,320 LIES ABOVE THE VOCAL FOLD. 1008 00:41:29,320 --> 00:41:32,600 SO, TWO DIFFERENT REPORTS IN THE 1009 00:41:32,600 --> 00:41:34,560 MOUSE HAVE SHOWN THAT THE 1010 00:41:34,560 --> 00:41:36,400 DEVELOPING VOCAL FOLD EPITHELIUM 1011 00:41:36,400 --> 00:41:38,480 NUMBER ONE IS STRATIFIED, YOU 1012 00:41:38,480 --> 00:41:40,800 CAN HIGHLIGHT THAT 1013 00:41:40,800 --> 00:41:42,160 STRATIFICATION WITH P63 IN A WAY 1014 00:41:42,160 --> 00:41:46,080 THE REST OF THE AIRWAY 1015 00:41:46,080 --> 00:41:48,640 EPITHELIUM IS NOT STRATIFIED. 1016 00:41:48,640 --> 00:41:54,400 AND THAT STRATIFIED EPITHELIUM 1017 00:41:54,400 --> 00:41:58,400 VERY SPECIFICALLY EXPRESSES -- 1018 00:41:58,400 --> 00:41:59,760 ACTIVATED PHOSPHO-YAP. 1019 00:41:59,760 --> 00:42:06,960 THAT'S ALSO IN THE TRUE IN THE 1020 00:42:06,960 --> 00:42:07,600 SYRINX. 1021 00:42:07,600 --> 00:42:08,240 P63, SIMPLE EPITHELIUM, 1022 00:42:08,240 --> 00:42:12,200 STRATIFIED SPECIFICALLY AT THE 1023 00:42:12,200 --> 00:42:16,320 SYRINX LEVEL. 1024 00:42:16,320 --> 00:42:18,200 IN ADDITION, PHOSPHORYLATED IN 1025 00:42:18,200 --> 00:42:22,320 THE CHICK VOCAL FOLD EPITHELIUM. 1026 00:42:22,320 --> 00:42:25,960 NOW, PHOSPHORYLATION OF YAP IS 1027 00:42:25,960 --> 00:42:27,840 NEXT TO THE CELLS EXPRESSING 1028 00:42:27,840 --> 00:42:29,920 RETINOIC ACID, PHOSPHORYLATION 1029 00:42:29,920 --> 00:42:30,560 MIGHT BE DEPENDENT ON RETINOIC 1030 00:42:30,560 --> 00:42:31,200 ACID. 1031 00:42:31,200 --> 00:42:33,720 IF YOU TREAT WITH INHIBITOR, 1032 00:42:33,720 --> 00:42:36,320 PHOSPHO-YAP GOES AWAY. 1033 00:42:36,320 --> 00:42:39,360 WE THINK PHOSPHO-YAP IS -- SO 1034 00:42:39,360 --> 00:42:42,160 THIS PART OF THE -- WE THINK BY 1035 00:42:42,160 --> 00:42:43,960 BRINGING IN RETINOIC ACID, 1036 00:42:43,960 --> 00:42:45,720 UPSTREAM REGULATOR, MAY BE ABLE 1037 00:42:45,720 --> 00:42:47,440 TO SIMULTANEOUSLY AFFECT THE 1038 00:42:47,440 --> 00:42:50,200 VOCAL TISSUE AND OVERLYING 1039 00:42:50,200 --> 00:42:52,160 EPITHELIUM MIMICKING THE PROGRAM 1040 00:42:52,160 --> 00:42:56,400 IN THE LARYNX, BRINGING IT TO 1041 00:42:56,400 --> 00:42:59,320 THE SYRINX. 1042 00:42:59,320 --> 00:43:00,400 SO RETINOIC ACID UPSTREAM FOR 1043 00:43:00,400 --> 00:43:02,360 PRELIMINARY, WE THINK WE HAVE 1044 00:43:02,360 --> 00:43:05,880 THIS NETWORK HERE IN THE LARYNX, 1045 00:43:05,880 --> 00:43:11,320 IN THE SYRINX, WE HAVEN'T SHOWN 1046 00:43:11,320 --> 00:43:12,200 RETINOIC ACID IS UPSTREAM IN THE 1047 00:43:12,200 --> 00:43:16,240 HOUSE WHERE -- MOUSE WHERE IT 1048 00:43:16,240 --> 00:43:23,760 IS IN THE CRICK SYRINX. 1049 00:43:23,760 --> 00:43:26,000 THIS IS THE UNDERLYING DEEP 1050 00:43:26,000 --> 00:43:27,800 HOMOLOGY IN EVOLUTION OF THE 1051 00:43:27,800 --> 00:43:28,120 SYRINX. 1052 00:43:28,120 --> 00:43:30,080 THE NEXT LITTLE BIT IS JUST THE 1053 00:43:30,080 --> 00:43:34,360 TWO SECONDS I WANT TO BE 1054 00:43:34,360 --> 00:43:36,000 SPECULATIVE HERE. 1055 00:43:36,000 --> 00:43:38,520 WE ARGUED SYRINX EVOLVED FROM 1056 00:43:38,520 --> 00:43:40,720 THE LARYNX BY CO-OPTING SOME 1057 00:43:40,720 --> 00:43:42,440 REGULATORY NETWORKS THAT WERE 1058 00:43:42,440 --> 00:43:43,200 THERE. 1059 00:43:43,200 --> 00:43:43,800 WHETHER DID THE REGULATORY 1060 00:43:43,800 --> 00:43:45,760 NETWORKS OF THE LARYNX COME 1061 00:43:45,760 --> 00:43:46,040 FROM? 1062 00:43:46,040 --> 00:43:47,400 WE WANT TO RAISE THE POSSIBILITY 1063 00:43:47,400 --> 00:43:52,280 THAT WAS BUILDING ON SOME EVEN 1064 00:43:52,280 --> 00:43:53,360 EARLIER REGULATORY NETWORKS, 1065 00:43:53,360 --> 00:43:56,600 WERE IT NOT FOR VIBRATORY FISH, 1066 00:43:56,600 --> 00:43:58,160 FLOPPY SORT OF MOVABLE TISSUE, 1067 00:43:58,160 --> 00:44:00,960 THAT'S IN THE HEART VALVES. 1068 00:44:00,960 --> 00:44:02,920 I SAY THAT BECAUSE IF YOU LOOK 1069 00:44:02,920 --> 00:44:06,400 IN THE CHICK, THE CHICK HEART 1070 00:44:06,400 --> 00:44:08,240 VALVE HAS EXPRESSION OF 1071 00:44:08,240 --> 00:44:11,200 EXTRACELLULAR MATRIX PROTEINS 1072 00:44:11,200 --> 00:44:12,240 AND SOX9, SIMILAR FASHION 1073 00:44:12,240 --> 00:44:14,400 REMINISCENTS OF WHAT WE SHOWED 1074 00:44:14,400 --> 00:44:17,240 IN VOCAL FOLDS OF CHICK AND 1075 00:44:17,240 --> 00:44:18,560 MOUSE, MOREOVER IN ZEBRAFISH 1076 00:44:18,560 --> 00:44:21,200 FROM OTHER PEOPLE'S WORK WE KNOW 1077 00:44:21,200 --> 00:44:24,800 RETINOIC ACID IS REQUIRED IN 1078 00:44:24,800 --> 00:44:34,120 HEART VALVE PRECURSORS, SOX9 IS 1079 00:44:34,120 --> 00:44:35,080 UPSTREAM OF RETINOIC ACID. 1080 00:44:35,080 --> 00:44:39,400 THEY SEEM TO BE PRESENT IN HEART 1081 00:44:39,400 --> 00:44:40,760 AND LARYNX, BOTH ALREADY AROUND 1082 00:44:40,760 --> 00:44:44,160 IN THE ANCESTOR OF BIRDS, THESE 1083 00:44:44,160 --> 00:44:45,200 WERE CO-OPTED, REGULATORY 1084 00:44:45,200 --> 00:44:50,040 NETWORK TO GIVE YOU THE SYRINX. 1085 00:44:50,040 --> 00:44:53,640 SO, FINALLY, TO JUST TELL YOU 1086 00:44:53,640 --> 00:44:55,000 THE SORT OF HIGHLIGHT -- TO 1087 00:44:55,000 --> 00:44:56,960 HIGHLIGHT WHAT YOU TOLD YOU, HOW 1088 00:44:56,960 --> 00:45:00,600 DID BIRDS EVOLVE CAPACITY TO 1089 00:45:00,600 --> 00:45:03,600 VOCALIZE, THEY BUILT A VOCAL 1090 00:45:03,600 --> 00:45:04,840 ORGAN FROM SCRATCH, OUT OF 1091 00:45:04,840 --> 00:45:05,840 CARTILAGE IN THE CHEST, GETTING 1092 00:45:05,840 --> 00:45:09,200 AROUND THE MAYHEM THAT NORMALLY 1093 00:45:09,200 --> 00:45:17,400 HAPPENS WHEN TURING MECHANISMS 1094 00:45:17,400 --> 00:45:20,560 SMASH INTO EACH OTHER, THROUGH 1095 00:45:20,560 --> 00:45:24,480 THE PROCESS OF RETRACTION OF 1096 00:45:24,480 --> 00:45:26,240 HEDGEHOG GRADIENT. 1097 00:45:26,240 --> 00:45:28,120 CO-OPTED FROM A VOCAL FOLD 1098 00:45:28,120 --> 00:45:31,400 PROGRAM IN THE LARYNX TO MAKE 1099 00:45:31,400 --> 00:45:34,000 VIBRATORY TISSUE. 1100 00:45:34,000 --> 00:45:34,840 THESE PROCESSES TOGETHER SORT OF 1101 00:45:34,840 --> 00:45:35,880 THE BEGINNING OF THE INROAD TO 1102 00:45:35,880 --> 00:45:38,200 TRY TO UNDERSTAND HOW YOU MAKE A 1103 00:45:38,200 --> 00:45:41,000 TRULY NOVEL STRUCTURE IN 1104 00:45:41,000 --> 00:45:41,640 EVOLUTION OF VOCALIZATION OF 1105 00:45:41,640 --> 00:45:42,000 BIRDS. 1106 00:45:42,000 --> 00:45:45,240 I WANT TO FINISH BY THANKENING 1107 00:45:45,240 --> 00:45:46,320 THE PEOPLE -- THANKING THE 1108 00:45:46,320 --> 00:45:49,520 PEOPLE WHO DID THE WORK. 1109 00:45:49,520 --> 00:45:54,800 EVAN KINGSLEY DID WORK ON THE 1110 00:45:54,800 --> 00:45:59,600 CART LAN, CHARLIE LONGTINE ON 1111 00:45:59,600 --> 00:46:03,640 TISSUE, JULIA CLARK AND FRANZ 1112 00:46:03,640 --> 00:46:05,400 GOLLER, BOTH WORKING ON OTHER 1113 00:46:05,400 --> 00:46:07,000 ASPECTS OF THE EVOLUTION OF THE 1114 00:46:07,000 --> 00:46:10,520 SYRINX AND FUNCTION OF THE 1115 00:46:10,520 --> 00:46:10,840 SYRINX. 1116 00:46:10,840 --> 00:46:13,120 I DIDN'T HAVE TIME TO TALK ABOUT 1117 00:46:13,120 --> 00:46:13,560 THAT. 1118 00:46:13,560 --> 00:46:17,280 FINALLY A SHOUT OUT TO MIKE 1119 00:46:17,280 --> 00:46:20,320 DYER, AT ST. JUDE IN TENNESSEE. 1120 00:46:20,320 --> 00:46:24,520 EVAN WAS A POSTDOC IN MY LAB. 1121 00:46:24,520 --> 00:46:26,800 AFTER HIS FIRST YEAR, HIS WIFE, 1122 00:46:26,800 --> 00:46:30,280 A HISTORIAN, THEY DON'T HAVE TO 1123 00:46:30,280 --> 00:46:32,640 DO POSTDOC, CAN GO STRAIGHT TO 1124 00:46:32,640 --> 00:46:34,320 FACULTY, GOT A JOB AFTER 1125 00:46:34,320 --> 00:46:36,520 GRADUATE SCHOOL, UNIVERSITY OF 1126 00:46:36,520 --> 00:46:37,960 MISSISSIPPI IN OXFORD. 1127 00:46:37,960 --> 00:46:39,280 THEY HAD A BABY. 1128 00:46:39,280 --> 00:46:40,600 EVAN DIDN'T WANT TO BE APART 1129 00:46:40,600 --> 00:46:43,440 FROM HIS WIFE BUT DIDN'T WANT TO 1130 00:46:43,440 --> 00:46:44,600 GIVE UP HIS PROJECT. 1131 00:46:44,600 --> 00:46:46,920 MIKE DYER DOES NOT WORK ON AVIAN 1132 00:46:46,920 --> 00:46:51,600 SYSTEM, HE WORKS ON MICE, ON 1133 00:46:51,600 --> 00:46:53,720 CANCER, GENEROUSLY GAVE US A 1134 00:46:53,720 --> 00:46:57,600 BENCH IN HIS LAB, ALLOWED EVAN 1135 00:46:57,600 --> 00:47:02,120 TO WORK AT ST. JUDE ON PROJECTS 1136 00:47:02,120 --> 00:47:04,480 FROM MY LAB, SATELLITE 1137 00:47:04,480 --> 00:47:04,760 OPERATION. 1138 00:47:04,760 --> 00:47:05,680 IF NOT FOR THAT GENEROSITY 1139 00:47:05,680 --> 00:47:08,960 COULDN'T HAVE DONE THE PROJECT. 1140 00:47:08,960 --> 00:47:11,280 I'LL STOP THERE AND TAKE ANY 1141 00:47:11,280 --> 00:47:12,640 QUESTIONS YOU WANT TO RELAY. 1142 00:47:12,640 --> 00:47:14,560 >> THANK YOU VERY MUCH. 1143 00:47:14,560 --> 00:47:18,760 THAT IS REALLY, REALLY 1144 00:47:18,760 --> 00:47:20,240 FASCINATING EVOLUTIONARY STORY 1145 00:47:20,240 --> 00:47:21,280 THERE. 1146 00:47:21,280 --> 00:47:22,800 BEFORE WE TAKE QUESTIONS, I'D 1147 00:47:22,800 --> 00:47:25,720 LIKE TO REMIND PEOPLE THAT ARE 1148 00:47:25,720 --> 00:47:27,600 APPLYING FOR CONTINUING MEDICAL 1149 00:47:27,600 --> 00:47:33,520 EDUCATION CREDITS THAT THE CME 1150 00:47:33,520 --> 00:47:38,400 CODE FOR TODAY IS 37935. 1151 00:47:38,400 --> 00:47:39,320 THAT'S 37935. 1152 00:47:39,320 --> 00:47:39,720 OKAY. 1153 00:47:39,720 --> 00:47:43,200 SO, OUR FIRST QUESTION COMES 1154 00:47:43,200 --> 00:47:44,400 FROM SUSAN. 1155 00:47:44,400 --> 00:47:47,960 SHE SAYS, HI, CLIFF, TERRIFIC 1156 00:47:47,960 --> 00:47:48,400 TALK. 1157 00:47:48,400 --> 00:47:50,360 ARE VOCAL CORDS -- FOLDS 1158 00:47:50,360 --> 00:47:51,920 UNIFORMLY ABSENT IN LARYNX OF 1159 00:47:51,920 --> 00:47:54,000 ALL BIRDS? 1160 00:47:54,000 --> 00:47:56,880 FOR EXAMPLE, DIVING BIRDS? 1161 00:47:56,880 --> 00:48:06,000 ANY CLUES ON HOW LARYNGEAL 1162 00:48:06,000 --> 00:48:08,880 FOLDS, CAN SOX9 INDUCE THEM? 1163 00:48:08,880 --> 00:48:10,320 >> SOX9 -- ONE AT A TIME. 1164 00:48:10,320 --> 00:48:14,360 ALL BIRDS THAT WE'VE LOOKED AT 1165 00:48:14,360 --> 00:48:15,680 HAVE -- ALL BIRDS DESCRIBED HAVE 1166 00:48:15,680 --> 00:48:18,600 A SYRINX AND NOT A LARYNX. 1167 00:48:18,600 --> 00:48:22,800 MY OWN LAB WE'VE DONE WORK ON 1168 00:48:22,800 --> 00:48:25,760 SOME LIKE OSTRICHES AND EMUS, 1169 00:48:25,760 --> 00:48:27,800 ONLY DIVING BIRD IS PENGUIN. 1170 00:48:27,800 --> 00:48:29,800 WE HAVE DATA ON BIRDS FROM MY 1171 00:48:29,800 --> 00:48:34,400 LAB, IT'S VERY WELL ESTABLISHED, 1172 00:48:34,400 --> 00:48:36,800 THE SYRINX -- BIRDS HAVE A 1173 00:48:36,800 --> 00:48:38,840 FUNCTIONAL SYRINX AND 1174 00:48:38,840 --> 00:48:40,280 NON-FUNCTIONAL LARYNX, 1175 00:48:40,280 --> 00:48:42,320 THROUGHOUT THE CROWN BIRDS. 1176 00:48:42,320 --> 00:48:44,560 WHETHER YOU CAN MAKE THE 1177 00:48:44,560 --> 00:48:46,640 LARYNX -- INDUCE THE LARYNX TO 1178 00:48:46,640 --> 00:48:49,360 HAVE VOCAL FOLDS, YOU CAN INDUCE 1179 00:48:49,360 --> 00:48:53,200 GENE EXPRESSION AT THE LEVEL OF 1180 00:48:53,200 --> 00:48:55,920 LARYNX BUT SORT OF DIDN'T 1181 00:48:55,920 --> 00:48:58,360 EMPHASIZE THE POINT, YOU GET 1182 00:48:58,360 --> 00:49:02,760 CELLULAR PROPERTIES WITHIN THE 1183 00:49:02,760 --> 00:49:09,200 TRACHEA, MISEXPRESS SOX 9 OR 1184 00:49:09,200 --> 00:49:11,400 RETINOIC ACID, THERE'S SWELLING, 1185 00:49:11,400 --> 00:49:14,600 TISSUE GETS THICKER AND NOT 1186 00:49:14,600 --> 00:49:15,240 SURPRISING, MAKE HYALURONIC 1187 00:49:15,240 --> 00:49:19,520 ACID, AND WE HAVE CHANGES IN 1188 00:49:19,520 --> 00:49:21,680 EPITHELIUM, STRATIFIED 1189 00:49:21,680 --> 00:49:23,160 EPITHELIUM, THE YAP, 1190 00:49:23,160 --> 00:49:24,200 PHOSPHO-YAP, CAN BE ACTIVATED. 1191 00:49:24,200 --> 00:49:28,480 YOU CAN DO ALL THAT WITHIN THE 1192 00:49:28,480 --> 00:49:31,280 LARYNGEAL REGION BUT THEY DO NOT 1193 00:49:31,280 --> 00:49:32,200 MAKE VIBRATORY TISSUE. 1194 00:49:32,200 --> 00:49:33,480 EVERYTHING I'VE TOLD YOU ABOUT 1195 00:49:33,480 --> 00:49:36,640 THIS REGULATION IS SUFFICIENT TO 1196 00:49:36,640 --> 00:49:38,440 GIVE YOU A THICKENED MESENCHYME, 1197 00:49:38,440 --> 00:49:42,560 SORT OF THE SOURCE OF THE 1198 00:49:42,560 --> 00:49:43,560 VIBRATORY TISSUE, SUBSEQUENT 1199 00:49:43,560 --> 00:49:44,600 DEVELOPMENTAL STEPS ARE NEEDED 1200 00:49:44,600 --> 00:49:46,920 TO TAKE THAT PATTERN TISSUE AND 1201 00:49:46,920 --> 00:49:48,840 TURN IT INTO VIBRATORY TISSUE. 1202 00:49:48,840 --> 00:49:49,800 WE'VE NOT DONE THAT IN THE 1203 00:49:49,800 --> 00:49:51,840 TRACHEA OR LARYNX OF THE BIRD. 1204 00:49:51,840 --> 00:49:54,000 HI TO YOU AS WELL, SUSAN. 1205 00:49:54,000 --> 00:49:56,440 HOPE TO TALK TO YOU SOON. 1206 00:49:56,440 --> 00:49:57,320 >> OKAY. 1207 00:49:57,320 --> 00:50:03,880 HERE IS A QUESTION FROM MARION 1208 00:50:03,880 --> 00:50:05,400 MARIAN YOUNG. 1209 00:50:05,400 --> 00:50:08,080 IS THE STRICTURE OF THE PHARYNX 1210 00:50:08,080 --> 00:50:13,520 DIFFERENT, THEIR -- I'M SORRY, 1211 00:50:13,520 --> 00:50:14,800 THE SCREEN IS CHANGING. 1212 00:50:14,800 --> 00:50:16,320 >> I'M TRYING TO GET OUT OF 1213 00:50:16,320 --> 00:50:19,160 SHARE SCREEN. 1214 00:50:19,160 --> 00:50:20,000 NOT SUCCESSFUL. 1215 00:50:20,000 --> 00:50:21,160 >> YEAH, MADE MY SCREEN BLINK 1216 00:50:21,160 --> 00:50:22,800 FOR A MOMENT. 1217 00:50:22,800 --> 00:50:26,360 MEN OFTEN HAVE LOWER VOICES THAN 1218 00:50:26,360 --> 00:50:26,560 WOMEN. 1219 00:50:26,560 --> 00:50:28,560 IS THE STRUCTURE OF THE SYRINX 1220 00:50:28,560 --> 00:50:30,000 DIFFERENT IN MALES AND FEMALES 1221 00:50:30,000 --> 00:50:33,600 IN THE BIRDS OR THEIR RESPONSE 1222 00:50:33,600 --> 00:50:37,080 TO RETINOIC ACID? 1223 00:50:37,080 --> 00:50:38,640 >> SO, ANOTHER PROJECT THAT'S 1224 00:50:38,640 --> 00:50:43,800 GOING ON IN MY LAB, I'M GOING TO 1225 00:50:43,800 --> 00:50:46,080 LEAVE IT LIKE THIS IF THAT'S 1226 00:50:46,080 --> 00:50:49,080 OKAY, ANOTHER PROJECT IN MY LAB 1227 00:50:49,080 --> 00:50:52,400 IS FOCUSING ON THE SYRINX OF THE 1228 00:50:52,400 --> 00:50:52,720 DUCK. 1229 00:50:52,720 --> 00:50:54,280 SO SHORT ANSWER, IF YOU LOOK IT 1230 00:50:54,280 --> 00:50:56,600 THE CHICK, NO DIFFERENCE BETWEEN 1231 00:50:56,600 --> 00:50:57,680 MALE AND FEMALE CHICK, OF COURSE 1232 00:50:57,680 --> 00:51:00,960 CHICKS WHEN THEY ARE BORN ARE 1233 00:51:00,960 --> 00:51:02,600 NOT SEXUALLY DIMORPHIC UNTIL 1234 00:51:02,600 --> 00:51:04,200 TESTOSTERONE HITS AT A LATER 1235 00:51:04,200 --> 00:51:06,200 STAGE, OR ESTROGEN KICKS IN. 1236 00:51:06,200 --> 00:51:08,560 EVEN IN ADULT SYRINX IT'S 1237 00:51:08,560 --> 00:51:09,640 SLIGHTLY DIFFERENT IN SIZE 1238 00:51:09,640 --> 00:51:10,760 BECAUSE ROOSTER IS BIGGER THAN 1239 00:51:10,760 --> 00:51:12,680 THE HEN, THEY ARE NOT DIFFERENT 1240 00:51:12,680 --> 00:51:14,040 IN FORM AT ALL. 1241 00:51:14,040 --> 00:51:16,560 IN THE DUCK, IT'S A VERY 1242 00:51:16,560 --> 00:51:19,280 INTERESTING STRUCTURE CALLED THE 1243 00:51:19,280 --> 00:51:20,880 BULLA, LIKE THIS OUTPOCKETING OF 1244 00:51:20,880 --> 00:51:23,640 THE SYRINX JUST ON ONE SIDE, ON 1245 00:51:23,640 --> 00:51:25,840 THE RIGHT-HAND SIDE, ONLY IN THE 1246 00:51:25,840 --> 00:51:27,160 MALE. 1247 00:51:27,160 --> 00:51:29,200 SO IT'S SEXUALLY DIMORPHIC, USED 1248 00:51:29,200 --> 00:51:31,440 TO MAKE A MATING WHISTLE. 1249 00:51:31,440 --> 00:51:33,720 SO LIKE A BOTTLE YOU BLOW AIR 1250 00:51:33,720 --> 00:51:34,640 ACROSS THE TOP. 1251 00:51:34,640 --> 00:51:39,280 IT'S WHAT THE BULLA IS USED FOR. 1252 00:51:39,280 --> 00:51:48,320 IT'S THE CONVERGENCE OF THE LEFT 1253 00:51:48,320 --> 00:51:50,200 ASYMMETRY PATHWAY, IT TURNS OUT 1254 00:51:50,200 --> 00:51:53,720 THE MALE ASYMMETRY IS THE 1255 00:51:53,720 --> 00:51:53,960 DEFAULT. 1256 00:51:53,960 --> 00:51:55,160 SO LEFT IN THE DUCK. 1257 00:51:55,160 --> 00:51:57,800 IF YOU DIDN'T HAVE ANY SEX 1258 00:51:57,800 --> 00:52:02,240 STEROIDS, YOU WOULD GET 1259 00:52:02,240 --> 00:52:03,880 ASYMMETRIC SYRINX, NO OTHERS 1260 00:52:03,880 --> 00:52:05,360 HAVE THAT EXCEPT DUCKS AND 1261 00:52:05,360 --> 00:52:09,120 RELATIVES GEESE AND SO ON. 1262 00:52:09,120 --> 00:52:20,560 IN THIS GROUP, MAKES ASYMMETRIC 1263 00:52:20,560 --> 00:52:22,640 SYRINX, THERE'S A CONVERGENCE, 1264 00:52:22,640 --> 00:52:25,720 THAT'S ONE CASE WITH SEXUAL 1265 00:52:25,720 --> 00:52:26,200 DIMORPHISM. 1266 00:52:26,200 --> 00:52:28,560 OTHER BIRDS ARE SEXUALLY 1267 00:52:28,560 --> 00:52:30,000 DIMORPHIC, JUST IN THICKNESS AND 1268 00:52:30,000 --> 00:52:31,800 SIZE OF TISSUE. 1269 00:52:31,800 --> 00:52:33,440 MALE AND FEMALE PARROTS HAVE 1270 00:52:33,440 --> 00:52:36,360 DIFFERENT SIZES, FOR INSTANCE. 1271 00:52:36,360 --> 00:52:40,280 BUT THEY DON'T HAVE THE 1272 00:52:40,280 --> 00:52:42,200 LEFT-RIGHT SYMMETRY OR 1273 00:52:42,200 --> 00:52:43,040 DIFFERENCE IN MORPHOLOGICAL 1274 00:52:43,040 --> 00:52:44,680 CHANGE. 1275 00:52:44,680 --> 00:52:45,120 >> OKAY. 1276 00:52:45,120 --> 00:52:46,960 ANOTHER QUESTION FROM DAVID 1277 00:52:46,960 --> 00:52:49,160 LEVIN, TERRIFIC TALK, HOW DOES 1278 00:52:49,160 --> 00:52:52,720 THE DEVELOPMENT, I'M NOT GOING 1279 00:52:52,720 --> 00:52:57,400 TO SAY THIS CORRECTLY, CECTASIAN 1280 00:52:57,400 --> 00:52:58,440 PHONIC LIPS COMPARE WITH SYRINX 1281 00:52:58,440 --> 00:53:01,800 OR LARYNX, IS IT A THIRD PATTERN 1282 00:53:01,800 --> 00:53:05,600 OR DERIVED FROM THE LARYNX? 1283 00:53:05,600 --> 00:53:08,880 >> I HAVE NO IDEA. 1284 00:53:08,880 --> 00:53:09,640 >> OKAY. 1285 00:53:09,640 --> 00:53:13,480 LET'S SEE. 1286 00:53:13,480 --> 00:53:21,680 FROM CHARLES SNYDERMAN, DO 1287 00:53:21,680 --> 00:53:26,800 TERASAURS A PHARYNX AND LARYNX. 1288 00:53:26,800 --> 00:53:31,880 >> THESE ARE CARTILAGE NOWS, NOT 1289 00:53:31,880 --> 00:53:32,080 BONE. 1290 00:53:32,080 --> 00:53:32,800 THEY DON'T FOSSILIZE WAY. 1291 00:53:32,800 --> 00:53:36,360 A FEW CASES YOU CAN GET 1292 00:53:36,360 --> 00:53:39,320 FOSSILIZED CARTILAGE, I SHOWED 1293 00:53:39,320 --> 00:53:42,600 YOU A CRUSTACEOUS BIRD. 1294 00:53:42,600 --> 00:53:46,200 OUR COLLABORATOR IS TRYING TO 1295 00:53:46,200 --> 00:53:47,960 FIND THAT. 1296 00:53:47,960 --> 00:53:51,040 GETTING A TERASAURS, ONE THING 1297 00:53:51,040 --> 00:53:52,160 THAT IMPLIES, DOES FLIGHT HAVE 1298 00:53:52,160 --> 00:53:53,520 SOMETHING TO DO WITH CHANGE IN 1299 00:53:53,520 --> 00:53:53,960 STRUCTURES. 1300 00:53:53,960 --> 00:53:54,280 IT'S POSSIBLE. 1301 00:53:54,280 --> 00:53:56,480 THERE ARE A NUMBER OF ARGUMENTS 1302 00:53:56,480 --> 00:54:00,840 FOR WHY THE LARYNX CHANGED USE, 1303 00:54:00,840 --> 00:54:03,080 REPLACED BY THE SYRINX, ONE OF 1304 00:54:03,080 --> 00:54:05,320 THE ARGUMENTS HAS TO DO WITH 1305 00:54:05,320 --> 00:54:08,600 SORT OF THE PHYSIOLOGY WHERE 1306 00:54:08,600 --> 00:54:10,400 SOME OF THE DINOSAUR AND 1307 00:54:10,400 --> 00:54:11,600 EARLYBIRDS HAD LONG NEXT, MAKING 1308 00:54:11,600 --> 00:54:14,360 A LOUD SOUND FROM SOMETHING WITH 1309 00:54:14,360 --> 00:54:17,680 THAT HIGH A STANDING WIND AIR 1310 00:54:17,680 --> 00:54:19,400 COLUMN WOULD BE DIFFICULT. 1311 00:54:19,400 --> 00:54:20,200 ONE OF THE OTHER ARGUMENTS, YOU 1312 00:54:20,200 --> 00:54:25,560 DO HAVE A CHANGE IN LOCATION OF 1313 00:54:25,560 --> 00:54:27,680 THE HYLOID BONE, CHANGE IN 1314 00:54:27,680 --> 00:54:28,560 BREATHING, FLIGHT ADAPTATIONS 1315 00:54:28,560 --> 00:54:29,680 THAT MAY HAVE MADE IT DIFFICULT 1316 00:54:29,680 --> 00:54:31,320 TO USE THE LARYNX FOR 1317 00:54:31,320 --> 00:54:38,640 VOCALIZATION IN WHICH CAUSE THE 1318 00:54:38,640 --> 00:54:41,360 TERASAUR MIGHT HAVE COME UP WITH 1319 00:54:41,360 --> 00:54:42,560 A YET A THIRD SOLUTION BUT WE 1320 00:54:42,560 --> 00:54:48,600 DON'T HAVE RECORDS OF THE AIRWAY 1321 00:54:48,600 --> 00:54:52,960 OF TERASAURS OR NON-AVIAN 1322 00:54:52,960 --> 00:54:53,360 DINOSAURS. 1323 00:54:53,360 --> 00:54:55,240 >> A QUESTION FROM CHRIS. 1324 00:54:55,240 --> 00:54:56,680 FASCINATING TALK. 1325 00:54:56,680 --> 00:54:58,680 IS THERE ANYTHING UNIQUE ABOUT 1326 00:54:58,680 --> 00:55:01,000 BIRD BIOLOGY SUCH AS FEATHERS 1327 00:55:01,000 --> 00:55:04,400 THAT WOULD HAVE STIFFENED THE 1328 00:55:04,400 --> 00:55:06,120 LARYNX VOCAL CORDS OTHERWISE 1329 00:55:06,120 --> 00:55:08,360 PREVENT THEM FROM EVOLVING TO 1330 00:55:08,360 --> 00:55:10,200 VIBRATE, OR IS THE SYRINX 1331 00:55:10,200 --> 00:55:12,160 ACTUALLY BETTER AT PRODUCING THE 1332 00:55:12,160 --> 00:55:17,320 RANGE OF SOUNDS IMPORTANT FOR 1333 00:55:17,320 --> 00:55:18,240 BIRD MATING? 1334 00:55:18,240 --> 00:55:21,680 >> SO, WHEN YOU SAY BETTER, I 1335 00:55:21,680 --> 00:55:25,080 THINK THE BIRDS NEED TO BE LOUD. 1336 00:55:25,080 --> 00:55:27,000 BECAUSE THEY HAVE TO BE LOUDER 1337 00:55:27,000 --> 00:55:28,480 THAN MAMMALS, BECAUSE THEY HAVE 1338 00:55:28,480 --> 00:55:30,960 TO COMMUNICATE OVER MUCH LONGER 1339 00:55:30,960 --> 00:55:32,800 DISTANCES, BECAUSE THEY CAN FLY 1340 00:55:32,800 --> 00:55:34,400 SO QUICKLY BETWEEN PLACES. 1341 00:55:34,400 --> 00:55:36,120 SO ONE OF THE THINGS THE SYRINX 1342 00:55:36,120 --> 00:55:37,680 HAS TO DO IS BE EFFICIENT. 1343 00:55:37,680 --> 00:55:45,440 MUCH MORE SO THAN THE LARYNX. 1344 00:55:45,440 --> 00:55:51,120 BUT THE -- BEYOND THAT, THERE'S 1345 00:55:51,120 --> 00:55:54,000 NOTHING ABOUT THE LARYNX 1346 00:55:54,000 --> 00:55:55,360 BECOMING STIFFER OR NOT WORKING, 1347 00:55:55,360 --> 00:55:57,000 BASICALLY EVERY ANIMAL THAT HAS 1348 00:55:57,000 --> 00:55:59,200 A LARYNX, EVERY LARYNX THAT HAS 1349 00:55:59,200 --> 00:56:01,960 A VOCAL CORD, VOCAL CORDS WORK 1350 00:56:01,960 --> 00:56:02,880 PERFECTLY WELL. 1351 00:56:02,880 --> 00:56:03,840 OPTIMIZE FOR THE ENVIRONMENT, 1352 00:56:03,840 --> 00:56:06,360 UNDER WATER, IN THE AIR, WHAT 1353 00:56:06,360 --> 00:56:06,840 HAVE YOU. 1354 00:56:06,840 --> 00:56:10,400 THEN YOU HAVE THE AVIAN LINEAGE, 1355 00:56:10,400 --> 00:56:13,800 TOTAL ABSENCE OF VOCAL CORDS, IN 1356 00:56:13,800 --> 00:56:16,480 THE LARYNX. 1357 00:56:16,480 --> 00:56:18,680 YOU COULD HYPOTHESIZE THAT YOU 1358 00:56:18,680 --> 00:56:20,000 CHANGE THE STRUCTURE IN THE 1359 00:56:20,000 --> 00:56:21,880 LARYNX AND THAT'S WHY IT BECAME 1360 00:56:21,880 --> 00:56:23,240 USELESS, AFTER IT WAS STIFF IT 1361 00:56:23,240 --> 00:56:24,200 WAS THEN LOST. 1362 00:56:24,200 --> 00:56:26,840 I'M NOT SURE HOW YOU TEST THAT. 1363 00:56:26,840 --> 00:56:29,320 BUT GIVEN -- THEY MAKE PERFECTLY 1364 00:56:29,320 --> 00:56:30,560 GOOD VIBRATING TISSUE IN THE 1365 00:56:30,560 --> 00:56:32,000 SYRINX, THERE'S NO REASON WHY 1366 00:56:32,000 --> 00:56:33,400 ANYTHING ABOUT A FEATHER PROGRAM 1367 00:56:33,400 --> 00:56:35,000 OR ANYTHING ELSE WOULD INTERFERE 1368 00:56:35,000 --> 00:56:36,320 WITH MAKING THE SOFT TISSUE IN 1369 00:56:36,320 --> 00:56:37,880 ONE PLACE AND NOT THE OTHER. 1370 00:56:37,880 --> 00:56:39,720 I WOULDN'T EXPECT THAT TO BE A 1371 00:56:39,720 --> 00:56:39,960 PROBLEM. 1372 00:56:39,960 --> 00:56:45,280 BUT THERE'S NO WAY TO TEST THAT. 1373 00:56:45,280 --> 00:56:46,920 >> REALLY FASCINATING ASPECT OF 1374 00:56:46,920 --> 00:56:49,680 YOUR TALK IS THE TURING 1375 00:56:49,680 --> 00:56:51,320 MECHANISM FORMING THE BANDS OF 1376 00:56:51,320 --> 00:56:51,680 CARTILAGE. 1377 00:56:51,680 --> 00:56:54,640 ARE YOU AWARE OF ANY OTHER 1378 00:56:54,640 --> 00:56:58,080 SYSTEM IN BIOLOGY THAT USES SUCH 1379 00:56:58,080 --> 00:57:01,040 A MECHANISM? 1380 00:57:01,040 --> 00:57:06,720 >> SO, A NUMBER OF CASES WHERE 1381 00:57:06,720 --> 00:57:10,200 YOU HAVE TURING MECHANISMS 1382 00:57:10,200 --> 00:57:11,680 PROPOSED FOR PATTERNS, 1383 00:57:11,680 --> 00:57:17,320 ESPECIALLY CODE PATTERNS, CICLID 1384 00:57:17,320 --> 00:57:20,560 FISH, ZEBRA STRIPING. 1385 00:57:20,560 --> 00:57:21,640 PERFECTLY PARALLEL STRIPES 1386 00:57:21,640 --> 00:57:24,280 PEOPLE HAVE NOT BEEN ABLE TO GET 1387 00:57:24,280 --> 00:57:31,920 OUT OF PURE TURING MECHANISMS, 1388 00:57:31,920 --> 00:57:33,000 THERE'S -- SHOOT. 1389 00:57:33,000 --> 00:57:35,040 BLOCKING ON SOMEONE'S NAME, IT'S 1390 00:57:35,040 --> 00:57:36,000 IMPORTANT, GIVE ME HALF A 1391 00:57:36,000 --> 00:57:47,560 SECOND. 1392 00:57:47,560 --> 00:57:54,840 I DEEPLY APOLOGIZE, BLOCKING ON 1393 00:57:54,840 --> 00:57:57,320 SOMEONE'S WORK AT PRINCETON, 1394 00:57:57,320 --> 00:57:59,360 UNPUBLISHED WORK, IT WOULDN'T 1395 00:57:59,360 --> 00:58:01,200 MAKES STRIPES BUT REQUIRED 1396 00:58:01,200 --> 00:58:02,360 ORTHOGONAL GRADIENT. 1397 00:58:02,360 --> 00:58:04,200 WORKS DIFFERENTLY THAN OURS 1398 00:58:04,200 --> 00:58:06,200 DOES, GROUND SQUIRRELS, SAME 1399 00:58:06,200 --> 00:58:11,320 RESULT. 1400 00:58:11,320 --> 00:58:11,600 >> OKAY. 1401 00:58:11,600 --> 00:58:13,240 >> LANERO LAB AT PRINCETON. 1402 00:58:13,240 --> 00:58:18,400 >> COULD YOU SAY THAT AGAIN. 1403 00:58:18,400 --> 00:58:21,000 >> MULINARO LAB AT PRINCETON. 1404 00:58:21,000 --> 00:58:21,640 >> GREAT. 1405 00:58:21,640 --> 00:58:22,400 >> SECOND INSTANCE WHERE 1406 00:58:22,400 --> 00:58:26,400 PARALLEL STRIPES WERE DERIVED 1407 00:58:26,400 --> 00:58:27,360 FROM TURING MECHANISM COULDN'T 1408 00:58:27,360 --> 00:58:30,200 DO IT WITHOUT A REFERENCE 1409 00:58:30,200 --> 00:58:31,200 GRADIENT, ALTHOUGH THE REFERENCE 1410 00:58:31,200 --> 00:58:33,880 GRADIENT IS DIFFERENT IN THAT 1411 00:58:33,880 --> 00:58:34,080 CASE. 1412 00:58:34,080 --> 00:58:37,200 >> ONE LAST QUESTION FROM TOM 1413 00:58:37,200 --> 00:58:37,720 SCHNEIDER. 1414 00:58:37,720 --> 00:58:41,760 DO VOICES DIFFER BECAUSE OF THE 1415 00:58:41,760 --> 00:58:43,720 IRREGULAR RINGS? 1416 00:58:43,720 --> 00:58:44,600 >> NO, BECAUSE THE IRREGULAR 1417 00:58:44,600 --> 00:58:45,840 RINGS ARE BELOW THE LARYNX. 1418 00:58:45,840 --> 00:58:50,080 THE LARYNX DOES NOT HAVE 1419 00:58:50,080 --> 00:58:50,440 IRREGULAR LINKS. 1420 00:58:50,440 --> 00:58:53,880 THEY ARE THE BRONCHIO TRACHEAL 1421 00:58:53,880 --> 00:58:55,520 JUNCTION, STILL HOLD THE AIRWAYS 1422 00:58:55,520 --> 00:58:55,760 OPEN. 1423 00:58:55,760 --> 00:58:58,480 ALL THAT MATTERS TO GET TO THE 1424 00:58:58,480 --> 00:59:00,200 LARYNX, SMOOTH LAMINAR AIR FLOW 1425 00:59:00,200 --> 00:59:01,360 THROUGH THE AIRWAY. 1426 00:59:01,360 --> 00:59:02,600 THE LARYNX ITSELF DOESN'T HAVE 1427 00:59:02,600 --> 00:59:03,120 THAT PROBLEM. 1428 00:59:03,120 --> 00:59:05,040 IT'S A LONG WAY FROM THE 1429 00:59:05,040 --> 00:59:08,680 BRONCHI. 1430 00:59:08,680 --> 00:59:08,960 >> OKAY. 1431 00:59:08,960 --> 00:59:09,400 LET'S SEE. 1432 00:59:09,400 --> 00:59:11,800 I THINK WE'RE OUT OF TIME, AT 1433 00:59:11,800 --> 00:59:13,680 THE MOMENT. 1434 00:59:13,680 --> 00:59:16,160 AND I WANT TO THANK YOU AGAIN. 1435 00:59:16,160 --> 00:59:17,800 THERE IS A FEW QUESTIONS IN THE 1436 00:59:17,800 --> 00:59:20,280 CHAT BOX THAT WE CAN SEND TO YOU 1437 00:59:20,280 --> 00:59:22,360 THAT PERHAPS YOU'LL HAVE A 1438 00:59:22,360 --> 00:59:23,040 CHANCE TO ANSWER. 1439 00:59:23,040 --> 00:59:26,160 BUT THANK YOU SO MUCH AGAIN FOR 1440 00:59:26,160 --> 00:59:26,440 JOINING US. 1441 00:59:26,440 --> 00:59:29,800 AND WE HOPE THAT YOU HAVE A GOOD 1442 00:59:29,800 --> 00:59:30,040 REST OF YOUR WEDNESDAY 1443 00:59:30,040 --> 00:59:31,000 AFTERNOON. 1444 00:59:31,000 --> 00:00:00,000 >>THANK FOR FOR INVITING ME.