368 



Special Vertebrate Organogenesis 



connective tissue). This characteristic dis- 

 tribution is grossly anticipated in the rela- 

 tive allocations of neurons to different pe- 

 ripheral sectors (see below, p. 374), in 

 the frequency of preterminal branching and 

 in the peripheral control of fasciculation. 

 Since this rough preallocation would still 

 leave a wide margin of variability in the 

 number of fibers actually arriving in a 

 tissue in a given individual, there are ad- 

 ditional screening factors in operation in the 

 terminal tissues themselves which adjust the 

 final quota of terminals to a stable norm. 

 Each tissue would thus maintain a char- 

 acteristic "saturation" density of irmerva- 

 tion. While not much is known about the 

 means by which this control is exerted, it 

 is already becoming obvious that they are 

 different for different tissues, and that the 

 mechanisms for upward regulation from a 

 deficient source are of a different kind than 

 those involved in the downward regulation 

 from an excessive source. They will there- 

 fore be considered separately. 



When supernumerary (Detwiler, '36b) or 

 excessively large (Harrison, '35a) limbs are 

 transplanted to the limb region of urodele 

 embryos, the enlarged periphery, while 

 causing no adaptive increase in the central 

 nerve source (see below, p. 382), yet de- 

 rives from that undersized source the full 

 contingent of nerve fiber branches appro- 

 priate to its larger mass. Similarly, limbs 

 transplanted in later larval stages, and 

 provided with only a small branch for re- 

 generative innervation, contain eventually 

 the full contingent of fibers normal for a 

 limb (Weiss, '37a). In nerve regeneration 

 in the adult, likewise, the nimiber of re- 

 generated fibers in the distal stumps approxi- 

 mates the normal quota, even if the prox- 

 imal source of fiber stems has been dras- 

 tically reduced (Dogliotti, '35; Litwiller, 

 '38a; Weiss and Campbell, '44; Billig, van 

 Harreveld and Wiersma, '46). 



This compensatory increase of the voltune 

 of innervation is due to more extensive 

 peripheral branching of the individual neu- 

 rons. Being the rule in the regeneration of 

 transected nerves (see above, p. 350), such 

 branching is satisfactorily accounted for in 

 the cases just mentioned in which nerves 

 have been severed. However, compensatory 

 branches may also arise, as if in response 

 to peripheral needs, from nerves that have 

 not been deliberately traumatized. When 

 musculature is partially denervated by the 

 experimental elimination of part of its tribu- 

 tary ventral roots, the residual healthy intra- 



muscular fibers develop "spontaneously" col- 

 lateral branches that take over the innerva- 

 tion of the neighboring denervated muscle 

 elements (see Edds, '53). The fact that such 

 collateral branching can be artificially in- 

 duced by intramuscular injection of extracts 

 from degenerating muscle (Hoffman, '52) 

 suggests an active participation of the de- 

 nervated muscle fibers in tapping the locally 

 available nerve sources for extra branches. 

 As indicated in our discussion of branching 

 mechanisms (p. 361), this need imply noth- 

 ing more than the weakening of the axonal 

 siuf ace, particularly at the nodes, to permit 

 ever-present abortive axonal leaks to yield 

 durable offshoots. Perhaps substances re- 

 ported to enhance nerve regeneration (von 

 Muralt, '46) should be viewed in the same 

 light, as facilitating the protrusion of 

 branches or diminishing the resistance of 

 tissues to penetration by them. 



Compensatory collateral innervation, com- 

 parable to that observed in muscle, has also 

 been described to occiu- in denervated sec- 

 tors of skin, whose infiltration by side 

 branches from nerves of the surrounding 

 intact area has been either observed di- 

 rectly in experimental cases (Weddell, Gutt- 

 mann and Gutmann, '41) or deduced from 

 clinical results (Livingston, '43). Again, 

 the explanation may lie either in a true 

 activation of branching by emanations from 

 the denervated tissue or, conversely, in the 

 removal of an active suppressing principle 

 that could be assumed to emanate from 

 nerve-saturated tissue as a bar to its invasion 

 by nerve branches continually forming as a 

 result of intra-axonal growth pressure and 

 surface instability. The latter alternative 

 seems plausible since the assumed abortive 

 branching has actually been observed in 

 living preparations (Speidel, '42). Negative 

 microscopic evidence, on the other hand, 

 would be meaningless in view of the elec- 

 tronmicroscopic demonstration of fiber col- 

 laterals far below the range of microscopic 

 visibility (Fernandez-Moran, '52). 



In conclusion, if overproduction of 

 branches is a regular occurrence, it would 

 account for a reservoir of fibers svifficiently 

 large to supply the needs of even a consid- 

 erably enlarged periphery; on the other 

 hand, it may be necessary in addition to 

 assume peripheral factors that facilitate, if 

 not the production, at least the fvuther out- 

 growth and consolidation, of branches in 

 accordance with the size of the periphery 

 to be innervated. Either mechanism insures 

 to the peripheral tissue a full quota of 



