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321 TABLE 61., .NEURAL TISSUE/NOTOCHORD RATIOS IN REGION,C Category Nurnbe¡. ... Mean . .... ..s. D, s. D.t'|. Controts t4 7.g't\29 1,7345g0 0.4635861 Normal Exptls. t0 6.gtgooo 1.767074 0.5587979 lilyetoschisls 11 5.510909 f:g66g60 0.5628795 l.lyelodysplasia 5 1,907999 O,31g1{;;z o.144176 Totat 40 6.206750 z.hgoos3 0.3937120 TABLE 62. ANALYSIs oF VARIANCE (RATIos) REGIoN c D. F. s.s. 1.1 . s - F. Between lr¡ rh in 3 36 1 39.340 102.474 \6.\\7 2.8\7 16.317 < 0.05 Tota I 39 241.814 BARTLETTIS TEST FOR REGION C Chi qq. D. F. P TABLE 6 Categor i es = 9.25\ =3 < 0.10 I'{ULTIPLE T- TS RAT I t G ION C D; F. Controls/Normal Expt¡ s. r.419 Contro I s/l'lye losch i s i s 3,209 Con t rol s/Mye I odyspl as i a 12.279 Normal Exptls./t'tyeloschísis 1,649 Normal Exp s. /Myelodysplas ia 8.502 Ìlyeloschlsís/l.tyelodysplas i a 6.1g1 19 21 15 r9 t0 1t N.S. P < 0.0,| P < 0.01 N.S. P < 0.01 P < 0.01
322 TABLE .64. ¡leunn|ilssue/norocro*o *ot'or''* REGtoN 0.. Category Number Hean . S. D. s . D. i,f. Cont rol s Normal Expt I s. Hye I os ch 1s i s l4yelodysplas îa Tota ¡ TABLE 65, ANALYSIS t4 t0 t1 5 4o OF VARIANCE 6.979286 1.704087 5,732000 1.2r5180 5.51\545 1.599928 2.593999 0. 478989 5.713999 1.959256 (RATros) REGtoN D 0,4554363 0.3842739 0.4823966 0.2142107 0.3097856 D. F. s.s. r't. s . F. P. Between 3 72.152 2\.051 1r.164 < 0.05 l'/i th i n 36 77.556 2.154 Tota I 39 149.709 BARTLETTIS TEST chí ôq. D. F. P FOR REGION D = 6.3\8 -) < 0.10 Categor ies Control s/Norma I Exp s. 2.o97 22 - N.S. Control s/Myel osch i s i s 2.218 22 N.S. Cont ro I s,/Mye I odysp ì as i a 8.779 t7 p < 0.01 Normal Exptl s. /Myeloschisis o.356 l8 N.S. Norma l Expt I s. /l'lye lodysp I as i a 7.161 13 P < 0.01 Ìlye losch i s i s,/l'lye I odysp I as i a 5.570 13 P < 0,01
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
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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
Page 141 and 142:
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
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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
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F¡ S. 33. Percentages Õf open cor
Page 157 and 158:
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
Page 163 and 164:
ì48 N=2ó4 ffi m Regulor Cord Defe
Page 165 and 166:
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
Page 171 and 172:
CERVICAT THORACIC LUMBAR FUSED CAUD
Page 173 and 174:
---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
Page 183 and 184:
-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
Page 224 and 225:
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'
Page 230 and 231:
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
Page 236 and 237:
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
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
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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
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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
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 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 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 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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