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117 lmm AT WINDOWING 2ó-30 HOURS STAGE 9' octS
Fi s. 22. lrregular open anteríor neuropore and trunk cysts in St. 11 embryo 1B hours after windowing. Fi g. 23. Establ ished open braîn defect and anophthalmia in St. 1B embryo 42 hours after windowing.
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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
Page 81 and 82: N=231 ffil e ooyi ffi s oays [il t2
Page 83 and 84: 6B TABLEt loj lloRTALtTy AFTER VtBR
Page 85 and 86: 70 5,3.2 Pa-rôf i Idì ¿irid PIè
Page 87 and 88: 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
Page 97 and 98: 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
Page 101 and 102: 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
Page 107 and 108: 92 TABLE 22. ¡¡UI'ISELTS OF PLATE
Page 109 and 110: 94 6.1 EMBRY0ûIIES I s 0L 0!!\- NE
Page 111 and 112: 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
Page 117 and 118: 421.. 26 25 I (3.85) 20 (76 .92) 1
Page 119 and 120: 00 N Eorly Deoths ,n -¡ F- ô- xu.
Page 121 and 122: 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: ligr. 21 - 30. Camera lucida drawin
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
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
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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
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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
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
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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
Page 306 and 307:
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
Page 346 and 347:
317 NEURAL TUBE-NOTOCHORD RATIOS IN
Page 348 and 349:
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
Page 364 and 365:
335 Lendon (1968, 1975) and notos (
Page 366 and 367:
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
Page 394 and 395:
365 APPENDIX B Stainl.ng of Carti l
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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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