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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
- Page 133 and 134: Fi s. 22. lrregular open anteríor
- Page 135 and 136: 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
- Page 141 and 142: t-l lmm IATER OPEN CORD DEFECT . RE
- Page 143 and 144: l2B t--l lmm EARLY OPEN CORD DEFECT
- Page 145 and 146: 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
- Page 153 and 154: 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
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- 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
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- 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
- Page 193 and 194: 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
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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
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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
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239 neural tissue ât the later sta
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241 The control group (Table 99 ) s
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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
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CDE D'E DE CDE DE DE DE D BCD BC BC
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TABLE q6,. STAGE 17-20 CoNTRoI AND
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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
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TABLE 47. CONTROL EMBRYoS.HISTOLOGI
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0 0 0 0 0 0 0 0 0 0 o 0 0 0 0 0 0 N
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42c 21 zo B c D E 0000 00 00 00 1\.
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l\t q\ 1oE 26 16 30E 59 16 3oE 77 1
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0 0 0 0 0 0 0 0 0 0 0 0 N) .{ Embry
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l\) \l N D E 00 00 0 0 13.79 0 100
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N) \¡ \2E 72 20 E B c D' E 00 0 15
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46. 15 76.92 0 20.51 14.83 2i,92 53
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ECTODERM DISCONTINUITY IN EXPERIMEN
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279 ECTODERM DISCONTINUITY IN EXPER
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SOMITE SEPARATION IN EXPERIMENTAL E
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283 NOTOCHORD SEPARATION IN EXPERIM
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285 SOMITE DEFECTS IN EXPERIMENTAL
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287 and distr¡bfrtíon in the cont
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19.09 r8.95 r 1.84 14.82 15.20 0 17
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0 15. 89 81 .08 100 100 ' 76.92 0 1
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43. rB 100 100 0 12.53 74.07 r00 't
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7.t6 16.03 100 100 160 7.90 18.22 r
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Figs. 120'123. Percentage ie.ngths
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299 O\TERLAP ZONE IN EXPERIMENTAL E
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301 OVERLAP ZONE IN EXPERIMENTAL EM
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303 ând every tenth sectlon was ne
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30c 12 16 c 17707,61 2463.3\ 7.19 D
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Ratio NT/N 4 .90 4.11 6.17 7.14 6.9
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Rêtlo NT/N 4.go \.36 3 .44 3. 18 3
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6.7t 6.lt 4.63 4.60 4.13 3.48 hzE 5
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Fi9s, 124-127, Neurál tube-norocho
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315 NEURAL TUBE -NOTOCHORD RATIOS I
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317 NEURAL TUBE-NOTOCHORD RATIOS IN
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319 TABLE 598 ' ANALYSIS OF VARIANC
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321 TABLE 61., .NEURAL TISSUE/NOTOC
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323 Apart f.rom the sîgnîficant d
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t25 7. Dlscusst0N 1'/i th progressi
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327 C¡osure of the anterior neurop
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329 the mid-polnts of the defects w
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331 'c¡osure of the neural folds w
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333 . These findings s.ugges r that
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335 Lendon (1968, 1975) and notos (
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337 Ferm, 1965; l"larin-Padi r ¡a,
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339 Kôplan (1965) and Kaplan and G
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341 reach the floor-plate; asymmetr
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343 took up the label, shovri.ng th
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345 The defects in early human embr
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347 after pred¡cted closure (Lemî
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349 hours could provide evidence fo
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351 t971), Gal lus and Xenopus (l'l
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353 1962i 1965). Barth and Barth.(1
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The result of any teratogen¡c insu
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357 Uindowîlg at ear¡y stages of
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SUHHARY AND CONCLUS I ONS
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361 separatlon between the neural p
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363 APPENDIX A Preparatlon of Early
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365 APPENDIX B Stainl.ng of Carti l
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367 10, BIBLIOGRAPHY, Alter, l.,l.
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369 Braun, l'{. (1882). entwicklung
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371 Crlley, B,B.(1969). Analysîs o
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373 dqs anomal ies de lrorganizatio
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375 Heath, H.D., Shear, H.H., lm€
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377 Jel inek, R. (1960). Developmen
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379 Laurence, K.14. (1964). Thé na
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381 McKeown, T. and Record, R.G.(19
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Penrose, L. S.(1957). Genetics of a
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385 Russell, H.E. and A¡ tken' G.T
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387 Spemann, H. (1938). Embryonic D
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389 lJeed, ¡.H. (1937 -38'). M.nin