376 



Special Vertebrate Organogenesis 



component processes of unequal kind and 

 weight, whose disparate contributions are 

 indistinguishably lumped in any bulk de- 

 termination. 



REGIONAL AND CYTOLOGICAL 

 DIFFERENTIATION 



Histochemistry of Differentiation. Superim- 

 posed upon the growth processes just dis- 

 cussed appear the cytological specializations 

 usually designated as "differentiations." It is 

 an axiom of development, however, that the 

 morphological (i.e., microscopically discern- 

 ible) "differentiation" of a cell (other than 

 trivial geometrical changes) is but the visible 

 expression of intimate changes in the compo- 

 sition and distribution of at least part of 

 the molecular population which constitutes 

 that cell (cf. Weiss, '49, '53). Any funda- 

 mental distinction between physicochemical 

 (sometimes called "physiological") and 

 morphological differentiation is thus purely 

 artificial, for it refers not to any dichotomy 

 in the properties of a cell but merely to two 

 different techniques of observation, both with 

 definite limitations, hence, supplementing 

 each other. Accordingly, marked differences 

 in morphology point to antecedent physico- 

 chemical changes, even though the latter 

 may not yet be detectable by our relatively 

 crude analytical tools, and conversely, de- 

 monstrable differences of physicochemical 

 constitution (including differential staining 

 in histological preparations) signify basic dif- 

 ferences of protoplasmic properties (cytodif- 

 ferentiation) even if these have failed to ex- 

 press themselves in corresponding differences 

 of structural detail. It is with these qualifica- 

 tions in mind that the results of correlated 

 studies between morphological and chemical 

 ontogeny of the nervous system should be 

 viewed (see also Section III, Chapter 1, by 

 Schmitt). 



A mental separation must be made between 

 those chemical systems that are common to 

 all cells (e.g., the ones engaged in respira- 

 tion, energy transfer, protein reproduction, 

 etc.) and those that are peculiar to the ner- 

 vous system. In practice, this is not feasible 

 because of the fragmentary state of our pres- 

 ent knowledge and because there are un- 

 doubtedly quantitative variations of the 

 former class which are as distinctive of nerve 

 cells as are qualitatively specific compounds. 

 Cytochemical studies of neuron growth have 

 already been referred to above (p. 365). Even 

 less is known about the specific biochemistry 

 of neural differentiation. 



Among the most profitable contributions 

 to this field have been studies on the develop- 

 ment of the cerebral cortex in which cyto- 

 logical, chemical, metabolic and functional 

 observations were correlated for a series of 

 sample stages. They have led to the recogni- 

 tion of certain critical phases during which 

 differentiation advances in spurts. Within the 

 same brief interval, the nucleus reaches 

 mature dimensions, Nissl bodies appear in 

 qvxantity, dendrites become more numerous, 

 nevirofibrils more prominent, the activities 

 of cytochrome c, adenylpyrophosphatase, and 

 succinic dehydrogenase rise sharply, and 

 electric brain potentials are recordable for 

 the first time (Flexner, '50). In amphibians, 

 motility develops in close parallelism with 

 the prodviction of acetylcholinesterase 

 (Youngstrom, '38; Sawyer, '43; Boell and 

 Shen, '50), which is instrumental in nerve 

 conduction, and experimental modifications 

 of the size of the brain (see p. 383) are 

 reflected in corresponding changes in its 

 content of these products (Boell and Shen, 

 '51). 



These examples may suffice to discourage 

 the practice of divorcing morphological from 

 underlying physicochemical considerations. 

 At the same time, much of this work must 

 still be counted in the descriptive class, fur- 

 nishing important data of irrformation but 

 not yet much causal understanding. 



Appearance of Regional Differences. As 

 mentioned above, different levels along the 

 longitudinal axis of the early CNS enter 

 different developmental courses, which subse- 

 quently express themselves in the overt 

 mosaic of morphological, histological, and 

 eventually, functional specializations. Al- 

 though some gross mosaic features may be 

 conceded to the neural plate from its very 

 first appearance (e.g., Nieuwkoop, '52; see 

 above, p. 370), its finer parcellation is a 

 continuing process the progress of which can 

 be tested by appropriate experiments (see 

 Section VI, Chapter 1, by Holtfreter and 

 Hamburger). The standard test consists of 

 displacing the part in question (by explanta- 

 tion, inversion, or heterotopic transplanta- 

 tion) in a graded series of stages and es- 

 tablishing precisely from what stage it can 

 carry on a course of development typical of 

 its original site even under aberrant environ- 

 mental conditions. 



This test presupposes that features attained 

 under the original and under the aberrant 

 conditions are sufficiently distinct to be used 

 as criteria. Individual blood cells, muscle 

 cells and pigment cells, for instance, can be 



