358 



Special Vertebrate Organogenesis 



guided toward the peripheral stump, not 

 by a chemical concentration gradient, but by 

 a structural bridge of Schwann cells which 

 has previously spanned the gap as a result 

 of the orienting "two-center effect" (see p. 

 354) which the two proliferating cut surfaces 

 exert upon the intervening blood clot. It is 

 easy to demonstrate this effect directly in 

 tissue culture (Fig. 131, bottom) by placing 

 two fragments of degenerated (axon-free) 

 peripheral nerve into a thin plasma clot 

 (Weiss, '52b). Evidently, if axons were to 



4-n 



Fig. 133. Deflection of peripheral limb nerve 

 plexus toward transplanted limb buds (combined 

 from Detwiler, '36b). The left half shows the plexus 

 of a normal forelimb (contribution from segments 

 3, 4, 5), the right half nerve supply in two experi- 

 mental cases in which limb buds had been trans- 

 planted from their norma] site (n) to anterior or 

 posterior levels, respectively, as indicated by arrows. 



grow from one of the stimips, the connecting 

 strand of Schwann cells would automatically 

 lead them over into the other stump. The 

 chemical activity of the degenerated stump 

 thus plays no part other than that of an 

 accessory aid to structural orientation. In 

 confirmation of this fact, degenerated nerve 

 in a liquid medium leaves nerve growth 

 wholly unaffected despite enhanced diffusion 

 (Weiss and Taylor, '44), and conversely, 

 oriented structural pathways are followed 

 by nerve fibers regardless of whether or not 

 they lead to supposedly "attractive" destina- 

 tions. For instance, when a proximal nerve 

 stump as fiber source is introduced into the 

 stem of a bifurcated blood-filled tube, one 

 branch of which contains degenerated nerve 

 while the other ends blindly (Fig. 132), 

 regenerating nerve fibers fill both branches 

 equally well and abundantly (Weiss and 

 Taylor, '44). 



In conclusion, the idea that remote tissues 

 of destination can attract nerve libers directly 

 may be safely discounted; such tissues do, 

 however, contribute to the formation of 

 nerve patterns indirectly by the creation of 

 pathways, as here outlined, as well as by 

 various secondary effects on later neuron 

 development to be detailed below. 



Ontogeny of Nerve Patterns. Our task is now 

 to explore whether what we have outlined 

 in the foregoing pages for nerve orientation 

 in general is sufficient to account adequately 

 for the specific nerve patterns observed in 

 the organism. 



Nerve Deflection Toward Growing Organs. 

 Evidence that embryonic nerve growth is 

 often actively routed toward rapidly growing 

 peripheral organs rests largely on the ex- 

 perimental work of Detwiler (summarized in 

 Detwiler, '36b). Transplanting urodele limb 

 buds, prior to the outgrowth of segmental 

 nerves, to farther anterior or posterior sites 

 entailed a certain shift of their nerve supply, 

 as is illustrated in Figure 133, which is a 

 composite of two typical cases. It can be seen 

 that there is a tendency for the limb plexus 

 to originate in more anterior or more poste- 

 rior segments than normally. Yet, since this 

 shift of the nerve source is less extensive than 

 the displacement of the limb, the nerve 

 trunks appear to slant forward or backward, 

 as if "attracted" by the actual limb site (see 

 also Lovell, '31). Svich deflection toward the 

 actively growing limb can readily be under- 

 stood as an instance of the "two-center effect" 

 outlined above. That the effect is quite un- 

 specific is demonstrated by the fact that the 

 limb nerves are similarly deflected toward 

 transplanted eyes and nasal placodes (Det- 

 wiler and Van Dyke, '34), although in the 

 latter case it has not been made clear how 

 much of the observed cord-nasal connection 

 originated in the cord and how much in 

 the olfactory epithelium. Brain grafts on the 

 other hand exert no such effect (Detwiler, 

 '36a), perhaps because the proliferating cell 

 layer is shut in and not exposed to the sur- 

 rounding matrix. 



Frog limb buds deprived of their ipsilateral 

 nerve source often secure vicarious supply 

 from the opposite side (Hamburger, '29). It 

 must be considered, however, that this is 

 initiated during an early stage, when both 

 hind limbs are still close together, and that 

 subsequent dislocations of the plexus and 

 fasciculation of the successful branches (see 

 below, p. 366) tend to create an exaggerated 

 idea of the power of nerves to reach their 

 destination by detours. 



