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l\) \l N D E 00 00 0 0 13.79 0 100 0 30E 69 16 30Ê 52 16 BCD B c D E B c D E 10.48 ß.93 o o 190 0 5\.17 0 00 14.7t 12.25 14.71 12.25 60.87 60.87 oo oo 0 0 0 0 0 0 0 0 4.s6 lo;07 o o 100 0 35.\2 o 100 0 12.75 18.55 2.70 2.81 100 0 r0o 28.57 100 0 t+28 I 17 42E ro 17 .B B c D E c D E 29.81 23.01 0 0 31 .87 o 00 gro 13,\4 9.24 o o 00 00 00 \3.\3 0 0 0 35.40 0 0 0 29.27 2\.33 0 15.63 0 0.88 65.93 o 100 22.22 100 0 0 20,96 0 0.92 77.46 o 100 13.64 100 0
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Page 1 and 2:
E}4BRYOGENES IS OF EXPERIHENTALLY I
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MY PARENTS c.J.H. G. M.
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lt Congenital malformêtlons of the
Page 7 and 8:
TABLE OF CONTENTS SECT ION PAGE 1 I
Page 9 and 10:
},I.ATE R I ALS 3.1 THE CHICK EI4BR
Page 11 and 12:
vt I I 6.3.2 Stage 10 Experímentel
Page 13 and 14:
9 APPENDTCES 378 APPENDIX A . 379 1
Page 15 and 16:
1.1 TERATOLOGY Birth defects have a
Page 17 and 18:
4 of the complexity of normal devel
Page 19 and 20:
6 flat, exposed plaque of neural ti
Page 21 and 22:
8 However, several early embryos in
Page 24 and 25:
.1- 5
Page 26 and 27:
l2 2.1 ErI0L0rL!! fïE qYs34t!1!!jr
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4 which has rema¡ned fairly consta
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6 and about 112 after two (Laure,nc
Page 32 and 33:
l8 ln some very early human embryos
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2l and kinky-ta¡l as disorders of
Page 37 and 38:
23 Vogel and McClenahan (1952) tnus
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I'IATE R IALS 25
Page 41 and 42:
27 lf necessary, eggs were stored a
Page 43:
FÍg. 5. lncubator allowing precise
Page 46 and 47:
3l 4. r sELEcr I oN !F EGGq 4.1,1 .
Page 48 and 49:
uler. Accurate Staging (Hamburger a
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.\lz '?. t
Page 52 and 53:
Fis. I AsB, Windowìng followed by
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Fis. 9 Aã8. t/indow?ng followed by
Page 57 and 58:
42 ( \--l /) ^ ) t0
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44 serîal sectlonlng a camera luci
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46 Thus the embryos selected for se
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48 TABLE 3. srAGE t0 El,tBRyos (cno
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50 TABLE 5 , Reg i ons srAGE 13:16'
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52 4.8.4 HistologÌcal_De:plþtÍon
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5 RESULTS OF TERAÎOLOGICAL PROCEDU
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(c) deaths and defects in the survi
Page 73 and 74:
Fi g. Percentagcs of early deaths a
Page 75 and 76:
6o MoRTALtTY, AFTER ì,'tNpowtNq,AT
Page 77 and 78:
TABLE B.'DEVEIOPI{ENT'AFTER'WINDOIi
Page 79 and 80:
TABLE 9. ¡4ALFORMATIONS PRODUCED'B
Page 81 and 82:
N=231 ffil e ooyi ffi s oays [il t2
Page 83 and 84:
6B TABLEt loj lloRTALtTy AFTER VtBR
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70 5,3.2 Pa-rôf i Idì ¿irid PIè
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TABLE 13; MALFORI4ATIONS AFTER PLAS
Page 89 and 90:
41 13 0 23 No l^l i ndow Control s
Page 91 and 92:
Fíg. Percentages of early deaths a
Page 93 and 94:
78 ALBUMEN INTRODUCTION Analysís o
Page 95 and 96:
0 1 0 0 a o TABLE 17. I'lALF0RÌ1AT
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N Eorly Deothi N=10ó N a ú, o d,
Page 99 and 100:
103 51 52 28 14 4 6 No W î ndow Co
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Fi g. 14. Percentages of early deat
Page 103 and 104:
88 AtR qELL, REEXPANSI0N Analysls o
Page 105 and 106:
90 5.4 BACTERt4L CUTTURE 0F UlNpohr
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92 TABLE 22. ¡¡UI'ISELTS OF PLATE
Page 109 and 110:
94 6.1 EMBRY0ûIIES I s 0L 0!!\- NE
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Fis. I5 A¿8, Range of s izes (mm.)
Page 113 and 114:
Figs. 16 AaB.. Range of sizes (mm.
Page 115 and 116:
100 6.1.2 f4ortal í!y with Vsrying
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421.. 26 25 I (3.85) 20 (76 .92) 1
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00 N Eorly Deoths ,n -¡ F- ô- xu.
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ì06 Degrees of Freedom 12 Chi Squa
Page 123 and 124:
hzE 53 42C z5 51(96.4)2\(96) 2(3.77
Page 125 and 126:
ffil Op"n Anterior Neuropore I I0 N
Page 127 and 128:
N=380 El Ovol Rhonnboid 'Sinus ì l
Page 129 and 130:
Øl Open Broin Defecls N=384 ffi F"
Page 131 and 132:
ligr. 21 - 30. Camera lucida drawin
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Fi s. 22. lrregular open anteríor
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lmm OPEN BRAIN DEFECT Á,NOPHTHALMI
Page 137 and 138:
lmm OVAL RHOMBOID S¡NUS 48 HOURS S
Page 139 and 140:
FiS. 26, Open neural folds extendin
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t-l lmm IATER OPEN CORD DEFECT . RE
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l2B t--l lmm EARLY OPEN CORD DEFECT
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Fis. 30. Large caudal cyst Ìn an o
Page 147 and 148:
132 6.1 .4 DeveloÞñent of oÞen N
Page 149 and 150:
Fig. 31 . Percentêges of experinen
Page 151 and 152:
36 TABLE ?8. RH0I4B0lD stNUs ctôs
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N=38o H ovol Rhomboid sinus l^ r38
Page 155 and 156:
F¡ S. 33. Percentages Õf open cor
Page 157 and 158:
142 6.1.5 Distríbution of 0pen Cor
Page 159 and 160:
Fi s. "l! Percentage distrìbution
Page 161 and 162:
lrregul ar (Z) somi te be low level
Page 163 and 164:
ì48 N=2ó4 ffi m Regulor Cord Defe
Page 165 and 166:
Fis. 36. Percentage distrîbution o
Page 167 and 168:
152 6.2 sPtIA! LFVELS 0F oPEN CORp
Page 169 and 170:
Fìgs. 37'38, Vertebral defecrs in
Page 171 and 172:
CERVICAT THORACIC LUMBAR FUSED CAUD
Page 173 and 174:
---l r r'I * 40
Page 175 and 176:
t59 a) spîna bif¡da occulta is se
Page 177 and 178:
:al . '**Ç- 4 ff, À(,) ftø 9-' o
Page 179 and 180:
162 lmnediately after closure, sepa
Page 181 and 182:
164 Hensenrs node and the primitive
Page 183 and 184:
-l :: l 48 I 49 i :. t: .lì 50 ì:
Page 185 and 186:
t67 somite area (through asymmetry
Page 187 and 188:
t69 ln both embryos the volume of n
Page 189 and 190:
171 The rhomblc roof became membran
Page 191 and 192:
173 At areas of myeloschisîs conta
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175 neurêl tîssue wíth mesoderm
Page 195 and 196:
t77 e) encroachment of somitîc mes
Page 197 and 198:
ôt rf) , ,,. ì _ ^iiir¡:ù\. I r
Page 199 and 200:
l 55 56 57 58 59 ó0
Page 202 and 203:
Fiss. 65 Early myeloschisis in a St
Page 204 and 205:
fiSr. 71 - 76. Later myeloschisis i
Page 206 and 207:
Fiss. 77 -82. Early myelodysplesia
Page 208 and 209:
FÌgs. B3 - BB. Later myelodysplas
Page 210 and 211:
Figs, 89 - 91. Processíng artifact
Page 212 and 213:
ì86 6.3.10 SequenJ¡¿il ll lúSti
Page 214 and 215:
Fígs. 95 - 102, Sequentiêl drawin
Page 216 and 217:
l9o EVERsToN: srAGE rf (o r o+) o @
Page 218 and 219:
@ @@ "@ @ e q q a a 192 CoNTROL: ST
Page 220 and 221:
MYELOSCHTSTS: STAGE tZ (tZeïl OOG
Page 222 and 223:
coNTRO[: STAGE tó (ro c zz) . a@ Q
Page 224 and 225:
G (õ--==: \z-- HEMTMYELIA: STAGE t
Page 226 and 227:
Som i te Defects contact none sePa
Page 228 and 229:
Somite Som i te Contact Defects N'
Page 230 and 231:
Som i te Contact Som i te Defects c
Page 232 and 233:
none none N) o o\ B r8c 23 12 good
Page 234 and 235:
separat ion none contact/ none sepa
Page 236 and 237:
Regíon Embryo Stage Conditîon Neu
Page 238 and 239:
none none none none none none l'.J
Page 240 and 241:
18E 10 13- vëry poor closed 0 cove
Page 242 and 243:
separãtion none contact none conta
Page 244 and 245:
Regíon Embryo Stage Condition Neur
Page 246 and 247:
separation none sepâ ra t îon non
Page 248 and 249:
separâtion none sepa ra t ion sepa
Page 250 and 251: Reglon Embryo Stagd cond¡t¡on Neu
Page 252 and 253: none none none none N) NJ .{ A A A
Page 254 and 255: contact/ none separatlon contact no
Page 256 and 257: Region Embryo Stage Conditlon Neura
Page 258 and 259: TABLE 38D. STAOE 17.20 CONTROL AND
Page 260 and 261: Reglon Embryo Stage Condition Neura
Page 262 and 263: 428 72 20 closed covered none conta
Page 264 and 265: 239 neural tissue ât the later sta
Page 266 and 267: 241 The control group (Table 99 ) s
Page 268 and 269: TABLE 39. APPEARANCE OF I,'HOLE EI4
Page 270 and 271: TABLE 40. APPEARANCE OF }/HOLE EI"I
Page 272 and 273: closed closed c I osed c I osed c I
Page 274 and 275: 249 6.6 pEVEL0PMENT 0F rH!_¡Ho|4gl
Page 276 and 277: Emb ryo Stage Rhombîc Roóf Neural
Page 278 and 279: CDE D'E DE CDE DE DE DE D BCD BC BC
Page 280 and 281: TABLE q6,. STAGE 17-20 CoNTRoI AND
Page 282 and 283: Figs- 10J - i11. Development of the
Page 284 and 285: Fî s. tub. Thick rhombic roof in 5
Page 286 and 287: Fig. 109 Hernbranous rhombic roof w
Page 288 and 289: 260 6.7 HrqroLoctcAL, cHANgË Assoc
Page 290 and 291: TABLE 47. CONTROL EMBRYoS.HISTOLOGI
Page 292 and 293: 0 0 0 0 0 0 0 0 0 0 o 0 0 0 0 0 0 N
Page 294 and 295: 42c 21 zo B c D E 0000 00 00 00 1\.
Page 296 and 297: l\t q\ 1oE 26 16 30E 59 16 3oE 77 1
Page 298 and 299: 0 0 0 0 0 0 0 0 0 0 0 0 N) .{ Embry
Page 302 and 303: N) \¡ \2E 72 20 E B c D' E 00 0 15
Page 304 and 305: 46. 15 76.92 0 20.51 14.83 2i,92 53
Page 306 and 307: ECTODERM DISCONTINUITY IN EXPERIMEN
Page 308 and 309: 279 ECTODERM DISCONTINUITY IN EXPER
Page 310 and 311: SOMITE SEPARATION IN EXPERIMENTAL E
Page 312 and 313: 283 NOTOCHORD SEPARATION IN EXPERIM
Page 314 and 315: 285 SOMITE DEFECTS IN EXPERIMENTAL
Page 316 and 317: 287 and distr¡bfrtíon in the cont
Page 318 and 319: 19.09 r8.95 r 1.84 14.82 15.20 0 17
Page 320 and 321: 0 15. 89 81 .08 100 100 ' 76.92 0 1
Page 322 and 323: 43. rB 100 100 0 12.53 74.07 r00 't
Page 324 and 325: 7.t6 16.03 100 100 160 7.90 18.22 r
Page 326 and 327: Figs. 120'123. Percentage ie.ngths
Page 328 and 329: 299 O\TERLAP ZONE IN EXPERIMENTAL E
Page 330 and 331: 301 OVERLAP ZONE IN EXPERIMENTAL EM
Page 332 and 333: 303 ând every tenth sectlon was ne
Page 334 and 335: 30c 12 16 c 17707,61 2463.3\ 7.19 D
Page 336 and 337: Ratio NT/N 4 .90 4.11 6.17 7.14 6.9
Page 338 and 339: Rêtlo NT/N 4.go \.36 3 .44 3. 18 3
Page 340 and 341: 6.7t 6.lt 4.63 4.60 4.13 3.48 hzE 5
Page 342 and 343: Fi9s, 124-127, Neurál tube-norocho
Page 344 and 345: 315 NEURAL TUBE -NOTOCHORD RATIOS I
Page 346 and 347: 317 NEURAL TUBE-NOTOCHORD RATIOS IN
Page 348 and 349: 319 TABLE 598 ' ANALYSIS OF VARIANC
Page 350 and 351:
321 TABLE 61., .NEURAL TISSUE/NOTOC
Page 352 and 353:
323 Apart f.rom the sîgnîficant d
Page 354 and 355:
t25 7. Dlscusst0N 1'/i th progressi
Page 356 and 357:
327 C¡osure of the anterior neurop
Page 358 and 359:
329 the mid-polnts of the defects w
Page 360 and 361:
331 'c¡osure of the neural folds w
Page 362 and 363:
333 . These findings s.ugges r that
Page 364 and 365:
335 Lendon (1968, 1975) and notos (
Page 366 and 367:
337 Ferm, 1965; l"larin-Padi r ¡a,
Page 368 and 369:
339 Kôplan (1965) and Kaplan and G
Page 370 and 371:
341 reach the floor-plate; asymmetr
Page 372 and 373:
343 took up the label, shovri.ng th
Page 374 and 375:
345 The defects in early human embr
Page 376 and 377:
347 after pred¡cted closure (Lemî
Page 378 and 379:
349 hours could provide evidence fo
Page 380 and 381:
351 t971), Gal lus and Xenopus (l'l
Page 382 and 383:
353 1962i 1965). Barth and Barth.(1
Page 384 and 385:
The result of any teratogen¡c insu
Page 386 and 387:
357 Uindowîlg at ear¡y stages of
Page 388 and 389:
SUHHARY AND CONCLUS I ONS
Page 390 and 391:
361 separatlon between the neural p
Page 392 and 393:
363 APPENDIX A Preparatlon of Early
Page 394 and 395:
365 APPENDIX B Stainl.ng of Carti l
Page 396 and 397:
367 10, BIBLIOGRAPHY, Alter, l.,l.
Page 398 and 399:
369 Braun, l'{. (1882). entwicklung
Page 400 and 401:
371 Crlley, B,B.(1969). Analysîs o
Page 402 and 403:
373 dqs anomal ies de lrorganizatio
Page 404 and 405:
375 Heath, H.D., Shear, H.H., lm€
Page 406 and 407:
377 Jel inek, R. (1960). Developmen
Page 408 and 409:
379 Laurence, K.14. (1964). Thé na
Page 410 and 411:
381 McKeown, T. and Record, R.G.(19
Page 412 and 413:
Penrose, L. S.(1957). Genetics of a
Page 414 and 415:
385 Russell, H.E. and A¡ tken' G.T
Page 416 and 417:
387 Spemann, H. (1938). Embryonic D
Page 418 and 419:
389 lJeed, ¡.H. (1937 -38'). M.nin
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