Nervous System 



381 



(p. 365) and the functional specialization 

 of centers by their end-organs discussed be- 

 low (p. 384), all of which add to our con- 

 viction that the potent role of the periphery 

 is exerted not by a single unitary mecha- 

 nism, but by a multiplicity of interlocking 

 ones. 



In the earlier studies of peripheral re- 

 bound on central development, attention was 

 focussed almost solely on the final size (niun- 

 ber of cells and total mass) of the affected 

 central part. Depending on whether it was 

 above or below the expected normal size 

 (mostly calculated from the asymmetry be- 

 tween the experimental and opposite control 

 halves of normally symmetrical systems), 

 the difference was described as "hyperplasia" 

 or "hypoplasia," signifying an overproduc- 

 tion or underproduction of cells. However, 

 since final size is determined not only by 

 proliferation rate but also by cell migration, 

 cell growth, cell destruction, etc (see above, 

 p. 375), these terms are apt to be misleading 

 and will not be used in the following dis- 

 cussion (see also Hamburger and Levi- 

 Montalcini, '49). When speaking of "periph- 

 ery," we shall mean tissues to be innervated, 

 not just any extra-neural environment. 



Peripheral Rebound on Primary Neurons. 

 Ganglia. No conspicuous excess of brachial 

 over trunk ganglia can be detected after 

 the respective peripheries have been roughly 

 equalized by the suppression of the develop- 

 ment of the limb (Detwiler, '24c; Hamburger 

 and Levi-Montalcini, '49). The intrinsic 

 development in the absence of a limb may 

 therefore be taken as the baseline over which 

 effects of peripheral increase build up. Sup- 

 pression of trunk muscles by myotomectomy 

 results in still smaller ganglia (Detwiler, 

 '27), but in view of the relative uniformity 

 of myotomes in the normal animal, this 

 fact can have no influence on the shape of 

 our "baseline." When a single limb develops 

 (i.e., in the normal case) there results then 

 a rise of this base value to the (normal) 

 magnitude typical of intact limb levels. 

 Adding a limb to a trunk segment raises 

 the base value of the latter so that the 

 spinal ganglia turn out larger than those 

 of normal trunk segments (Detwiler, '20; 

 Hamburger, '39b). In amphibians, the effect 

 can be obtained throughout the larval stages 

 until after metamorphosis (Carpenter, '32, 

 '33). Cranial ganglia likewise enlarge when 

 they are made to innervate a supernumerary 

 organ grafted to the head (Detwiler, '30b). 

 These increases are only partly due to in- 

 creased proliferation; for the most part they 



result from the fact that more of the "in- 

 different" neuroblasts (see above, p. 380) 

 in the ganglion are caused to mature into 

 large typical dorsal root neurons (Hambur- 

 ger and Levi-Montalcini, '49), which thus 

 add not only to the tally of identifiable 

 sensory cells, but being larger, also to the 

 mass of the ganglion. Besides, there occurs 

 normally in various ganglia a certain 

 amount of cell degeneration, which in the 

 presence of a larger periphery, e.g., a limb, 

 is held in check (Hamburger and Levi- 

 Montalcini, '49). Thus, the final coimt of 

 cells is regulated through at least three de- 

 vices: proliferation, maturation and elimina- 

 tion. 



Whether the effect is of a generalized 

 kind, involving all neurons of the overloaded 

 region, or a selective response of specifically 

 matching types is still an open question. 

 That there is some selectivity is definitely 

 indicated by the ganglionic response to tu- 

 mor transplantation. Ganglia at the level 

 of a transplanted mouse sarcoma (in chick 

 embryos) show the typical increase com- 

 monly observed under conditions of periph- 

 eral overload (Bueker, '48). The effect is 

 selective in that it exempts the motoneurons 

 of the cord, remains confined to the medio- 

 dorsal neurons in the spinal ganglia, and 

 reaches its greatest intensity in the purely 

 sympathetic para- and prevertebral ganglia 

 (Levi-Montalcini and Hamburger, '51, '53). 



This whole problem has recently been 

 complicated by the discovery that the sym- 

 pathetic ganglia of the chick embryo develop 

 excessively even when the inducing sarcoma 

 graft has been placed on the allantoic mem- 

 brane, beyond the reach of actual fiber con- 

 nections, evidently exerting its effect by 

 some humoral agent (Levi-Montalcini, '52; 

 Levi-Montalcini and Hamburger, '53). One 

 could tentatively assume that the primary 

 effect of the tumor agent consists of a gen- 

 eral unstabilization of cell surfaces. The 

 nerve cell bodies would thereby be enabled 

 to issue more sprouts, and the nerve fibers 

 more branches (see above, p. 361); this effect 

 has actually been observed in tissue culture 

 (Levi-Montalcini et al., '54). The visceral 

 organs, on the other hand, would lose their 

 surface protection against fiber invasion and 

 could absorb the outgrowing branches (see p. 

 370). But the relation, if any, between these 

 events and the ganglionic hyperplasia is 

 by no means clear, and the factual analysis 

 will have to be driven much further before 

 any definitive explanation can be adopted. 



Spinal Cord. As in the spinal ganglia, the 



