380 



Special Vertebrate Organogenesis 



older embryos, definite cell types would be- 

 gin to be missing in otherwise morphologi- 

 cally well restituted halves, with the large 

 motor cells dropping out first, commissural 

 neurons next and general internuncials last 

 (Holtzer, '51). This indicates that the re- 

 generated cell types stem each from the 

 homologous cell type of the intact half; that 

 the various types lose their mobility or be- 

 come otherwise unavailable as sources of 

 replacement, one by one, in the observed 

 time sequence; and that the descendent 

 cells of different strains can no longer sub- 

 stitute for one another. 



If this be the case, the term "indifferent," 

 commonly given to cells of no particular 

 morphological distinctiveness, is misleading. 

 Actually, these cells would constitute a 

 heterogeneous population, each with defi- 

 nite differential type characteristics, which 

 may or may never come to the fully mature 

 expression amenable to morphological classi- 

 fication; they would not be a common pool 

 of truly equivalent elements, which could 

 still be switched into the various types of 

 specific neurons by determinative local influ- 

 ences. It is by no means unlikely that eventu- 

 ally both assumptions (a) and (b) will turn 

 out to be partly correct in the sense that 

 some distinctive type specificity is already 

 inherent in the cells leaving the gernunal 

 layer for the mantle, but that additional di- 

 versity is imposed upon them by conditions 

 along their path and at their final locations. 



The appearance of qualitative diversity 

 among sensory neurons has also been dem- 

 onstrated for the spinal ganglia. Aside from 

 indirect deductions from the fact of selec- 

 tive fasciculation (see above, p. 366), tangi- 

 ble microscopic, topographical and be- 

 havioral differences between cell groups 

 subserving different functions have been 

 revealed imder the microscope (Levi-Mon- 

 talcini and Levi, '43); as will be shown 

 below, they likewise represent qualitatively 

 different segments of a heterogeneous neviron 

 population. 



In conclusion, there is ample evidence for 

 the early emergence in the CNS of quali- 

 tatively diverse cell strains, the number of 

 recognized varieties being severely limited 

 by the inadequacy of our means of dis- 

 crimination; there is some evidence that the 

 diversity of strains can at least partly be 

 projected right back to a corresponding di- 

 versity within their production source, the 

 neural epithelium; and that this mode of 

 development of qualitative regional diversity 

 leaves an adequate margin for quantitative 



adjustments of numbers within each type — 

 the adjustments which will form the sub- 

 ject of the following pages. 



PERIPHERAL EFFECTS ON CENTRAL 

 DEVELOPMENT 



Historical Remarks. A quantitative corre- 

 spondence between nerve centers and their 

 peripheral area of innervation has long been 

 inferred from comparative and pathological 

 studies. Congenital absence of an extremity, 

 for instance, was found to be reflected in uni- 

 lateral underdevelopment of the correspond- 

 ing spinal segments (e.g., Edinger, '21). 

 However, whether the missing parts had 

 failed to develop from the start or had been 

 formed but secondarily degenerated from 

 lack of peripheral outlets could not be de- 

 cided by such static observations. The first 

 attempt to reproduce the results experi- 

 mentally by removing limb buds in chick 

 embryos (Shorey, '09) led essentially to a 

 confirmation of the fact that centers faced 

 with a reduced periphery became (or re- 

 mained) undersized; they also proved that 

 the relation was a causal one, without, how- 

 ever, elucidating its nature. In further cor- 

 roboration, removal of an eye in early am- 

 phibian larvae was found to entail reduced 

 size of the optic centers in the corresponding 

 (i.e., contralateral) midbrain hemisphere 

 (Steinitz, '06; Durken, '13). Yet, not until 

 these defect experiments were supplemented 

 by overloading experiments could the ac- 

 tively stimulating nature of the peripheral 

 influence be regarded as firmly established. 

 The first well attested case was the ex- 

 cessive development of spinal ganglia in 

 trunk segments whose peripheral mass had 

 been increased by the addition of a grafted 

 limb (Detwiler, '20). Continued experimen- 

 tation in amphibians (chiefly by Detwiler 

 and his school), and later even more pene- 

 tratingly in birds (by Hamburger and co- 

 workers), has reiterated an old lesson of 

 biological research: a relation that on first 

 acquaintance appears simple and transpar- 

 ent, when subject to more minute analysis 

 more often than not turns out to be much 

 more complex, if not more obscure, than 

 originally suspected. Significant differences 

 were discovered in the response of different 

 species, of spinal ganglia vs. spinal cord, 

 between brain parts, and among different 

 regions of the cord. Meanwhile, other types 

 of peripheral influences upon central de- 

 velopment have been discovered, such as 

 the control of neuronal size reported above 



