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6.7t 6.lt 4.63 4.60 4.13 3.48 hzE 57 428 65 CD c D c D c D 4oqo9. r 3 2\661 .93 18039.2\ 13392.88 17414.\2 12851 .82 6020.97 3908.29 3897.63 ?914.10 4216.91 3694.39
(u2 ) Ratio NT/N 1.72 2,33 2.19 2.79 1.99 3. t9 2.22 1 .92 r .47 2.6\ Embryo S tage Reg ions of Regions of Les icin l'leasu remen ts Mean Neural Tissue (u2 ) Hean Notochord 30Ê. 35 308 76 16 16 hzl 52 17 4zE So 18 \zE 56 l8 BC BCDE BC BC DE BC DE c D c D c D c D c 3815.57 52\3.32 5674.14 6299.43 7921 .52 7090.52 9066.77 181\.45 7177.\7 2219.02 2252.72 2595.16 2261 .37 4077.35 222\.38 4084 .47 4060.84 4890. 1 I D 10131 .55 4r 46.40
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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
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TABLE OF CONTENTS SECT ION PAGE 1 I
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},I.ATE R I ALS 3.1 THE CHICK EI4BR
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vt I I 6.3.2 Stage 10 Experímentel
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9 APPENDTCES 378 APPENDIX A . 379 1
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1.1 TERATOLOGY Birth defects have a
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4 of the complexity of normal devel
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6 flat, exposed plaque of neural ti
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8 However, several early embryos in
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.1- 5
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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
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l8 ln some very early human embryos
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2l and kinky-ta¡l as disorders of
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23 Vogel and McClenahan (1952) tnus
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I'IATE R IALS 25
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27 lf necessary, eggs were stored a
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FÍg. 5. lncubator allowing precise
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3l 4. r sELEcr I oN !F EGGq 4.1,1 .
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uler. Accurate Staging (Hamburger a
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.\lz '?. t
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Fis. I AsB, Windowìng followed by
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Fis. 9 Aã8. t/indow?ng followed by
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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
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Fi g. Percentagcs of early deaths a
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6o MoRTALtTY, AFTER ì,'tNpowtNq,AT
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TABLE B.'DEVEIOPI{ENT'AFTER'WINDOIi
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TABLE 9. ¡4ALFORMATIONS PRODUCED'B
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N=231 ffil e ooyi ffi s oays [il t2
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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
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41 13 0 23 No l^l i ndow Control s
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Fíg. Percentages of early deaths a
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78 ALBUMEN INTRODUCTION Analysís o
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0 1 0 0 a o TABLE 17. I'lALF0RÌ1AT
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N Eorly Deothi N=10ó N a ú, o d,
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103 51 52 28 14 4 6 No W î ndow Co
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Fi g. 14. Percentages of early deat
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88 AtR qELL, REEXPANSI0N Analysls o
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90 5.4 BACTERt4L CUTTURE 0F UlNpohr
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92 TABLE 22. ¡¡UI'ISELTS OF PLATE
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94 6.1 EMBRY0ûIIES I s 0L 0!!\- NE
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Fis. I5 A¿8, Range of s izes (mm.)
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Figs. 16 AaB.. Range of sizes (mm.
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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
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hzE 53 42C z5 51(96.4)2\(96) 2(3.77
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ffil Op"n Anterior Neuropore I I0 N
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N=380 El Ovol Rhonnboid 'Sinus ì l
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Øl Open Broin Defecls N=384 ffi F"
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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
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lmm OVAL RHOMBOID S¡NUS 48 HOURS S
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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
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132 6.1 .4 DeveloÞñent of oÞen N
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Fig. 31 . Percentêges of experinen
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36 TABLE ?8. RH0I4B0lD stNUs ctôs
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N=38o H ovol Rhomboid sinus l^ r38
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F¡ S. 33. Percentages Õf open cor
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142 6.1.5 Distríbution of 0pen Cor
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Fi s. "l! Percentage distrìbution
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lrregul ar (Z) somi te be low level
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ì48 N=2ó4 ffi m Regulor Cord Defe
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Fis. 36. Percentage distrîbution o
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152 6.2 sPtIA! LFVELS 0F oPEN CORp
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Fìgs. 37'38, Vertebral defecrs in
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CERVICAT THORACIC LUMBAR FUSED CAUD
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---l r r'I * 40
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t59 a) spîna bif¡da occulta is se
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:al . '**Ç- 4 ff, À(,) ftø 9-' o
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162 lmnediately after closure, sepa
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164 Hensenrs node and the primitive
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-l :: l 48 I 49 i :. t: .lì 50 ì:
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t67 somite area (through asymmetry
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t69 ln both embryos the volume of n
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171 The rhomblc roof became membran
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173 At areas of myeloschisîs conta
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175 neurêl tîssue wíth mesoderm
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t77 e) encroachment of somitîc mes
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ôt rf) , ,,. ì _ ^iiir¡:ù\. I r
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l 55 56 57 58 59 ó0
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Fiss. 65 Early myeloschisis in a St
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fiSr. 71 - 76. Later myeloschisis i
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Fiss. 77 -82. Early myelodysplesia
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FÌgs. B3 - BB. Later myelodysplas
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Figs, 89 - 91. Processíng artifact
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ì86 6.3.10 SequenJ¡¿il ll lúSti
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Fígs. 95 - 102, Sequentiêl drawin
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l9o EVERsToN: srAGE rf (o r o+) o @
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@ @@ "@ @ e q q a a 192 CoNTROL: ST
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MYELOSCHTSTS: STAGE tZ (tZeïl OOG
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coNTRO[: STAGE tó (ro c zz) . a@ Q
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G (õ--==: \z-- HEMTMYELIA: STAGE t
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Som i te Defects contact none sePa
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Somite Som i te Contact Defects N'
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Som i te Contact Som i te Defects c
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none none N) o o\ B r8c 23 12 good
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separat ion none contact/ none sepa
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Regíon Embryo Stage Conditîon Neu
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none none none none none none l'.J
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18E 10 13- vëry poor closed 0 cove
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separãtion none contact none conta
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Regíon Embryo Stage Condition Neur
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separation none sepâ ra t îon non
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separâtion none sepa ra t ion sepa
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Reglon Embryo Stagd cond¡t¡on Neu
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none none none none N) NJ .{ A A A
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contact/ none separatlon contact no
Page 256 and 257:
Region Embryo Stage Conditlon Neura
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TABLE 38D. STAOE 17.20 CONTROL AND
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Reglon Embryo Stage Condition Neura
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428 72 20 closed covered none conta
Page 264 and 265:
239 neural tissue ât the later sta
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241 The control group (Table 99 ) s
Page 268 and 269:
TABLE 39. APPEARANCE OF I,'HOLE EI4
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TABLE 40. APPEARANCE OF }/HOLE EI"I
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closed closed c I osed c I osed c I
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249 6.6 pEVEL0PMENT 0F rH!_¡Ho|4gl
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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
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Fî s. tub. Thick rhombic roof in 5
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Fig. 109 Hernbranous rhombic roof w
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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 300 and 301: l\) \l N D E 00 00 0 0 13.79 0 100
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 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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