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Special Vertebrate Organogenesis 



the secretion of fluid from the cells of the 

 inner lining of the early ventricles (Weiss, 

 '34b; Holtzer, '51). Furthermore, the ciliary- 

 beat of the lining may propel the fluid 

 anteriorly, which in the normal embryo 

 would help to maintain the distention of 

 the brain cavity. In cyclostomes and teleosts, 

 in which the CNS is laid down initially as 

 a solid cell cord, this same secretion process 

 seems to be the method by which the central 

 lumen is secondarily established in the in- 

 terior. The shrinkage of the central canal 

 by partial fusion of its walls (see Ham- 

 burger, '48), paralleled by the decline of 

 mitotic activity, may reflect a reduction of 

 turgor in the spinal portion. 



With hydrostatic pressixre on the inside 

 and the confining skull capsule on the out- 

 side, continued enlargement of the brain 

 wall by growth, cell migrations and the de- 

 position of white matter must be expected 

 to lead to deformations, which, depending 

 on the local conditions, manifest themselves 

 as cave-ins, outpocketings, fissures or folds. 

 Practically nothing is known about the me- 

 chanics of these elementary shaping proc- 

 esses, although there are at least some indi- 

 cations that the fissures between major di- 

 visions of the cortex actually arise as cave-ins 

 along lines of least resistance in the wall 

 which tends to expand in confined space 

 (Clark, '45; Kallen, '51). It must be empha- 

 sized, however, that the systematic pattern, 

 according to which such mechanical events 

 take place, is intrinsically prepared by the 

 inequalities established previously by the 

 locally differing processes of proliferation, 

 migration, aggregation and differentiation 

 (see Bergquist and Kallen, '53a); the gross 

 mechanical factors do not create these dif- 

 ferentials, but merely translate them into 

 more conspicuous spatial configurations. 



Accordingly, the attainment of normal 

 brain configuration depends not only on the 

 typical development of the brain wall, but 

 also on the proper harmony between the 

 latter and the growth of the skvill capsule 

 (or in the case of the cord, the spine) on 

 the outside, and the turgor of the cerebro- 

 spinal liquor on the inside. If this harmony 

 is disturbed, either by a genetically deter- 

 mined imbalance between the component 

 tissues or by later trauma or nutritional 

 deficiencies, serious aberrations of the CNS 

 will ensue. Genetically conditioned hyper- 

 secretion of central fluid, for instance, leads 

 to hydrocephalus and brain herniation (Lit- 

 tle and Bagg, '24; Bonnevie, '34; see Section 



XIV, Teratogenesis, by Zwilling); delayed 

 closure of the folds past the onset of secre- 

 tion, to various grades of spina bifida with 

 draining fistulae (for an example of me- 

 chanical production of spina bifida, see Fow- 

 ler, '53); and retardation of skull growth 

 in vitamin A deficiency, with unimpeded 

 growth of the CNS, to brain compression 

 and herniation (Wolbach and Bessey, '42). 

 The early cartilaginous capsule, at least 

 in the spinal region, can accommodate its 

 size to the actual dimensions of the en- 

 closed CNS (Holtzer, '52a), but this adapt- 

 ability is certainly greatly reduced in later 

 stages. 



Morphogenesis of the Neural Crest. The 

 neural crest, which contains precursor cells 

 for spinal ganglia, sympathetic ganglia, 

 Schwann cells, pigment cells, and, in lower 

 vertebrates, also branchial skeleton and 

 ordinary mesenchyme, is regionally spe- 

 cialized even before its cells start on their 

 migrations away from the dorsal midline 

 (Horstadius, '50; Niu, '47). The bilateral 

 cell masses first move down in rather co- 

 herent sheets (Detwiler, '37b); the parts of 

 prime interest here, those giving rise to 

 the ganglia, then settle down in two major 

 columns, one between spinal cord and myo- 

 tomes, the other alongside the aorta, with 

 further outposts moving into the viscera. 

 The localization of the ganglionic columns 

 is hardly a simple matter of filling open 

 grooves between the tissues, but rather an 

 expression of specific contact affinities be- 

 tween the crest cells and the surrounding 

 cell systems. We find a model of this 

 process in the formation of pigment bands 

 bv neural crest-derived melanophores 

 (Twitty, '49), where the migrating cells 

 likewise aggregate along certain tracts pre- 

 formed in the surrounding tissues. 



Later the continuous colvimns break up 

 into segmental clusters. The tendency to 

 separate into smaller groups seems to be 

 intrinsic to the cells, but the segmental 

 localization of these groups is determined 

 by the segmental arrangement of the myo- 

 tomes, for the experimental removal Cor 

 disarrangement) of the latter abolishes (or 

 correspondingly disarranges) the segmental 

 array of the ganglia (Lehmann, '27; Det- 

 wiler, '34, '35). The segmental arrangement 

 of the nerve roots and neural arches is 

 likewise dependent on the presence of axial 

 mesoderm (Detwiler, '37b), but just how 

 these processes are causally interrelated is 

 not yet clear. 



