362 



Special Vertebrate Organogenesis 



in comparable experiments in urodeles: Det- 

 wiler, '36a), spinal fiber tracts into limbs 

 (Nicholas, '29; Weiss, '50a), limb nerves into 

 tumors (Bvieker, '48; Levi-Montalcini and 

 Hamburger, '51), optic nerves into the nose 

 (Weiss, '41c) or the pharynx (Ferreira- 

 Berutti, '51). 



Yet, the peripheral nervous system of 

 normal individuals is relatively stereotyped, 

 not only in the mode of its arborization but 

 also in its terminal connections. By and 

 large, ventral root fibers end in skeletal 

 muscles, spinal ganglion fibers in sensory 

 end organs, sympathetic fibers in glands or 

 smooth muscles. Since the attempts to refer 

 this specificity of connections to selective 

 neurotropic attractions have proved unten- 

 able, other explanations must be sought. 



Mindful of the fact that the first outgrowth 

 of motor fibers antedates that of sensory 

 fibers (Coghill, '29), it has been suggested 

 (Harrison, '35b; Weiss, '39) that a systematic 

 change in the peripheral pathway structure, 

 with the earlier pathways leading to muscles, 

 the later ones to skin, would automatically 

 account for the correct routing. However, 

 this time-lag explanation is ruled out by the 

 observation that motor and sensory fibers 

 take each their typical courses even when 

 both grow out simultaneously, as for in- 

 stance, in the innervation of the hind limb 

 of the anuran tadpole. When the bud makes 

 its late appearance, both motor and sensory 

 nerve masses are already waiting at its base 

 ready to invade it (Taylor, '43). As they 

 penetrate the limb bud, they assort them- 

 selves according to kinds into specifically 

 muscular and cutaneous branches, respec- 

 tively, coursing sometimes jointly, but often 

 also independently. This has been revealed 

 by withholding either the sensory or the 

 motor nerve quota from the limb (Ham- 

 burger, '29), and most conclusively by ex- 

 tirpating the appropriate spinal ganglia or 

 spinal cord segments (Taylor, '44); the 

 developed limbs then lacked the correspond- 

 ing kind of nerve branches. 



It seems difficult to account for these facts 

 otherwise than by the assumption of selec- 

 tive contact affinities of given nerve fiber 

 types for matching types of preneural path- 

 ways. This view is strengthened by the pre- 

 dilection which nerves with aberrant origins 

 or courses show for their typical sites or 

 channels, as has been described for the 

 lateral line nerve (Harrison, '03), the dorsal 

 roots (Detwiler and Maclean, '40; Holtzer, 

 '52b), and Mauthner's fibers (Oppenheimer, 

 '41; Piatt, '44; Stefanelli, '50; Holtzer, '52b). 

 Such selective application of one tissue to 



another is not uncommon in development 

 (see, for instance, the guided growth of the 

 pronephric duct; Holtfreter, '44); but, save 

 for a hypothetical reference to its possible 

 stereochemical basis (Weiss, '47), the under- 

 lying mechanism is still obscure. 



Specificity in Regeneration. The ability of 

 given kinds of nerve fibers to select con- 

 forming pathways seems to last beyond the 

 pioneering phase. After transection of the 

 mixed nerves to a young differentiating limb, 

 the regenerating motor fibers retrace essen- 

 tially the original mviscular branches, and 

 the regenerating sensory fibers the cutaneous 

 branches (Taylor, '44). Similarly, regenerat- 

 ing lateral line nerves have been reported to 

 give preference to an old lateral line branch 

 over a nearby cutaneous branch (Speidel, '48), 

 which even suggests finer subspecificities 

 within the sensory class. Yet, with the prog- 

 ress of maturation, this selectivity of out- 

 growth is lost. Adult nerves of different 

 qualities, when cross-connected, regenerate 

 into each other's channels indiscriminately 

 and without difficulty. For example, sensory 

 fibers regenerate into motor stumps (Boeke, 

 '17; Gutmann, '45; Weiss and Edds, '45) and 

 vice versa (Weiss and Cummings, '43), 

 somatic nerves into sympathetic stumps and 

 vice versa (Simpson and Young, '45; Ham- 

 mond and Hinsey, '45), etc. Apparently, the 

 residual Schwann cords of degenerated 

 stumps, which serve as pathways to the re- 

 generating fibers, are of the same quality in 

 motor, sensory, somatic and autonomic 

 nerves, hence are indistinguishable to the 

 regenerating fibers, which, as will be shown 

 below, have not lost their constitutional dif- 

 ferentials. 



Terminal Connections. Nerve fibers may 

 reach the peripheral tissues either preassorted 

 over proper pathways or intermingled over 

 aberrant routes (see above), but neither mode 

 of approach is decisive for whether or not 

 they will make transmissive connections, 

 that is, connections which will permit im- 

 pulses to pass between nerve fiber and end 

 organ. A clear distinction must be made be- 

 tween {a) penetration of a tissue by nerve 

 fibers ("neurotization"), {b) microscopic 

 contiguity between nerve ending and effector 

 or receptor cell, and (c) physiologically effec- 

 tive junction. No absolute specificity prevails 

 in («) and (Z>), but (c) occurs only if end- 

 organ and nerve fiber are generally related. 



For example, when sensory nerve fibers are 

 led into muscles, they terminate on the 

 muscle fibers in what histologically appear 

 to be intimate motor connections (Boeke, 

 '17); yet electric stimulation of such nerves 



