382 



Special Vertebrate Organogenesis 



peripheral rebound on the development of 

 the spinal cord is superimposed upon an 

 intrinsic pattern of regional differences (see 

 p. 374), which may again serve as "base- 

 line." Even without limbs, this baseline is 

 higher in limb segments than in cervical 

 and thoracic segments (Bueker, '43; Ham- 

 burger, '46). As for its potential altera- 

 tion by changes in peripheral area, the 

 results seemed at first to vary according to 

 species. In urodeles, the presence of a limb 

 caused no increase in the number of cells 

 in the "motor" half of the respective cord 

 region (Detwiler, '24c), although in accord- 

 ance with the conclusions reported under 

 Factors Controlling Neuron Growth, p. 365, 

 the individual neurons, hence the cross sec- 

 tions of the motor roots, were larger (Det- 

 wiler and Lewis, '25). In anurans (May, 

 '33) and birds (Hamburger, '34), on the 

 other hand, the presence of a limb entailed a 

 considerable enlargement of the "motor" 

 cell columns of the cord. This apparent 

 discrepancy turned out to be one of ter- 

 minology. Whereas in the latter group the 

 large cell bodies of motoneurons are com- 

 pactly assembled in separate cell columns 

 ("motor horns") and therefore can be tal- 

 lied separately, in urodeles they lie inter- 

 mingled with other cell types so that for 

 practical reasons the total number of cells 

 in the ventral half of the cord was counted 

 as "motor." Subsequent cell counts in the 

 chick (Hamburger and Keefe, '44) showed 

 that in this form likewise the total cell num- 

 bers in the ventral cord were not appreciably 

 different whether or not a limb was there, 

 but that in the presence of one, the ratio 

 of "indifferent" to fully matured motor horn 

 cells was shifted in favor of the latter, and 

 only the latter had been counted in the 

 earlier studies. 



It is clear from these facts that one of the 

 effects of the actual presence of a limb in 

 the limb segments is a recruitment process 

 by which neuroblasts that would otherwise 

 have remained less distinctive are induced 

 to mature into large motoneurons. However, 

 this is only part of the story. First, there 

 seems to be also a certain, though minor, 

 stimulation of (mitotic) cell proliferation 

 (Hamburger and Keefe, '44); why this does 

 not lead to an increased cell number in 

 cases with overloaded peripheries has not 

 been resolved. Second, the ways in which 

 the "baseline" values are attained in dif- 

 ferent regions vary markedly and the ways 

 of the peripheral influences vary accordingly. 

 As outlined before (p. 378), in the chick the 



various levels of the spinal cord, initially 

 of comparable cell content, gradually assume 

 unequal sizes owing to increased cell degen- 

 eration in the cervical region, increased 

 maturation of ventral horn cells in the 

 brachial region, and characteristic migra- 

 tions of the cell bodies (or just the nuclei?) 

 of preganglionic sympathetic and parasym- 

 pathetic neurons in the thoracic and sacral 

 regions, respectively (Levi-Montalcini, '50) 

 (see Fig. 141). A limb added to any of these 

 regions will then cause segmental enlarge- 

 ment by either reducing degeneration, or 

 promoting maturation, or checking emigra- 

 tion, respectively. 



This diversity of ways in which the final 

 cell tally can be altered complicates the 

 search for the underlying mechanisms and 

 raises doubts in the assumption of a single 

 common mechanism. As in the case of the 

 spinal ganglia, one could maintain that it 

 takes a primary connection between a center 

 and its peripheral district by some pioneer- 

 ing fibers in order to furnish that center 

 with an estimate of its peripheral domain. 

 But how does the pioneering neiiron con- 

 vey its information to others still in im- 

 mature state? We have already commented 

 on those changes in metabolic activity and 

 other properties of a successfully connected 

 neuron that express themselves in its size 

 (p. 365) and fasciculation (p. 366). One 

 need only assume that certain effects of these 

 changes spread to neighboring cells (Ham- 

 burger, '39b; Hamburger and Keefe, '44). 

 Observations in sheep embryos, showing co- 

 incidence between the arrival of motoneu- 

 rons at the periphery and the development 

 of their dendritic fields, have led to the 

 contention that spreading dendrites might 

 be the transmitters of the inducing stimulus 

 (Barron, '43, '46). But this explains little. 

 For one thing, it coiild not apply to spinal 

 ganglion cells, which lack dendritic inter- 

 connections, and moreover, the unknown 

 influence becomes no better known by being 

 transferred from the perikaryon to the den- 

 drites. 



The nimierical increase of peripherally 

 overloaded centers is limited by the output 

 capacity of the respective centers. Thus, 

 whereas the addition of a limb produces a 

 marked increase over the limbless state, the 

 further addition of one, two or even three 

 extra limbs to the plexus fails to produce an 

 appreciable further augmentation (Verzar 

 and Weiss, '30; Weiss, '37a; Bueker, '45). 

 It is perhaps for this reason that large limbs 

 transplanted orthotopically to a small body 



