370 



Special Vertebrate Organogenesis 



be responsible for the great local differences 

 in the density of the central neuropil (see 

 Herrick, '48, pp. 29-39). 



It is interesting to note, in this connection, 

 that topical application of carcinogens en- 

 tails a marked rise in the density of the 

 local cutaneous nerve net (Julius, '30), and 

 that the presence of mouse sarcomata in 

 chick embryos similarly opens certain vis- 

 ceral organs, e.g., the mesonephros, which 

 normally would have remained uninner- 

 vated, to profuse invasion by sympathetic 

 fibers (Levi-Montalcini and Hamburger, 

 '53). These observations seem to indicate 

 that the mechanisms controlling saturation 

 density can be suspended by certain agents, 

 among which tumor agents seem to be 

 prominent. 



The peripheral density control (Fig. 137), 

 whatever its nature may be, serves to in- 

 sure, in combination with the other numeri- 

 cal controls outlined earlier, the attainment 

 and maintenance of an adequate fimctional 

 state despite wide fluctuations of the indi- 

 vidual developmental histories. It should 

 have become clear from our discvxssion that 

 such pvirportedly goal-directed performances, 

 when properly analyzed, are resolvable into 

 chains of causal mechanisms. 



DEVELOPMENT OF THE CENTRAL 

 NERVOUS SYSTEM (CNS) 



DETERMINATION OF THE CNS 



The foregoing chapters, devoted to nerve 

 fibers, have taken the existence of nerve 

 cells for granted. To consider the origin 

 of the nerve cells themselves, we must now 

 turn back to an earlier phase of the em- 

 bryonic history. As for the manner in which 

 neural differentiation is initiated and the 

 primordia of the neural system are mapped 

 out in the early embryo, we may simply 

 refer to the article in this book by Holt- 

 freter and Hamburger. We shall take up 

 the story from the time when the antero- 

 dorsal sector of the ectoderm has become 

 irrevocably earmarked for the formation of 

 the neural organs and endowed with the 

 capacity to produce parts with the morpho- 

 logical, histological and chemical charac- 

 teristics of central nervous system even 

 when isolated from the rest of the germ. At 

 that stage, by virtue of anteceding inter- 

 actions of induction and segregation, the 

 neural plate has become constituted as a 

 system of fields, the median ones directing 

 the transformation to central nervous struc- 

 tures — anteriorly, brain and its derivatives; 



posteriorly, spinal cord — while the marginal 

 ones give rise to neural crest. That this area 

 already has biochemical properties that are 

 distinctly neural is indicated by its selective 

 immune response to antibodies prepared 

 against adult neural antigens (Ebert, '50). 

 At least in anteroposterior direction, it con- 

 stitutes a definite mosaic of fields (Dalcq, 

 '47; Nieuwkoop, '52), the individual re- 

 gions of which already contain differential 

 conditions guiding the subsequent steps of 

 morphogenesis toward the formation of spe- 

 cific localized parts of the CNS. It is these 

 steps, involving mainly folding, cell move- 

 ments, proliferation, cell growth, cytodif- 

 ferentiation, secretion, and cell degeneration, 

 that we shall now consider in greater detail. 



EARLY MORPHOGENESIS 



Neurulation. Transformation of the neural 

 plate into the neural tube occurs by means 

 of forces residing within the plate itself, 

 for as was shown by Roux (1895), the fold- 

 ing takes place even in excised and isolated 

 plates. The expansive pressure of the sur- 

 rounding epidermis in the germ plays 

 merely an adjuvant role (Giersberg, '24). 

 The dynamics of the folding process, as 

 those of similar invaginations (e.g., gastru- 

 lation; see article by Costello in this book) 

 are still not fully understood. They are 

 based on the development of differences in 

 surface expanse between the outer and inner 

 sides of the plate. An earlier suggestion, 

 attributing this difference to differential 

 water uptake (Glaser, '14), has now been 

 discounted (Glaser, '16; Brown, Hamburger 

 and Schmitt, '41). Differential cell growth 

 or cell multiplication has likewise been ruled 

 out (Burt, '43b; Gillette, '44; Hutchinson, 

 '44). The most likely assumption is that of 

 an active contraction of the outer surface 

 of the plate, the contractile elements, pre- 

 sumably fiber proteins, being either in the 

 cells (Lewis, '47) or in their oviter coating 

 (Holtfreter, '43), or perhaps in the inter- 

 cellular fiber cement around the outer cell 

 poles seen under the microscope as "terminal 

 web" (Sauer, '35). Active elongation of 

 the medullary cells may normally assist this 

 process (Brown, Hamburger and Schmitt, 

 '41; Holtfreter, '46); ultraviolet irradiation 

 of the germ with wave lengths near the 

 absorption maximum of sterols inhibits it 

 (Davis, '44). 



When the raised folds meet from the two 

 sides, epidermis fuses with epidermis, and 

 neural layer with neural layer. Since this 



