388 



Special Vertebrate Organogenesis 



the two species differ crucially. So far, 

 heteroplastic work has dealt largely with 

 the former. The limbs of a given species 

 of salamander are readily controlled by limb 

 spinal cord of another species, no matter 

 whether the strange combination is etlected 

 by transplanting the limb to the foreign 

 host (Detwiler, 30a; Twitty and Schwind, 

 '61; Hari'ison, o5a) or by substituting foreign 

 limb cord segments for those of the host 

 (Wieman, '25; Detwiler, '31); even newt 

 cord can coordinate salamander leg function 

 (Hertwig, '26). But then, activities do not 

 differ markedly between these species. The 

 exchange of limbs between anurans and 

 urodeles should be more rewarding, since 

 the combination is feasible (Guyenot, '27), 

 and one could test whether or not a urodele 

 center can make a frog leg jump. Recent 

 studies on the behavior of animals with 

 hybrid vestibular organs show clearly the 

 great potentialities of such research (An- 

 dres, '45). 



Taking all these sketchy fragments of in- 

 formation together, the conclusion emerges 

 that spinal cord and brain develop early a 

 gross topographic mosaic of functionally 

 specialized areas, each with specific physico- 

 chemical and structural peculiarities not 

 fully shared by the others, whereas each 

 sector of this mosaic within itself manifests 

 wide powers of regulation and substitution; 

 so much so that any theory of coordination 

 that would rely on a rigidly predetermined 

 order of microconnections among neurons 

 (rather than merely statistical regularities) 

 seems clearly controverted by the facts of 

 experimental embryology. It is highly in- 

 structive that these embryological data paral- 

 lel closely the results of work on functional 

 localization in the cortex, which have like- 

 wise revealed macrolocalization of func- 

 tional districts without microlocalization on 

 the cellular level (Lashley, '42). It is in 

 problems of this kind that embryology, 

 physiology and psychology become confluent 

 so that a conjoint approach promises to lead 

 to much deeper insight than we now pos- 

 sess.* The techniques of experimental mor- 

 phology, able to manufacture crucial test 

 situations in young animals never attainable 

 in the adult, have hardly yet been called 

 upon to contribute their share to this team- 

 work. Their exploitation seems to hold rich 

 prizes, but space restrictions do not permit 

 us to elaborate the matter in this place. 



* See the Survey of Neurobiology; Publication 

 No. 237 by the National Academy of Sciences-Na- 

 tional Research Council, Washington, D. C, 1952. 



THE HUMORAL MILIEU IN NEURAL 

 DEVELOPMENT 



It is beyond the scope of this article to 

 review the specific nutrient requirements of 

 the various components of neurogenesis. As 

 in other organ development, the internal 

 milieu must provide not only all factors 

 requisite for general cell life, growth and 

 difterentiation, but must in addition satisfy 

 the more specialized needs of the countless 

 steps of which "tlie development of the ner- 

 vous system" is composed. Even in its early 

 formative stage, the CNS is already distin- 

 guished from other organ rudiments by its 

 different metabolic requirements (Spratt, 

 '52). Neuropathology, on the other hand, 

 has been able to trace many neural defects 

 of the adult to deficiencies in the availabil- 

 ity or utilization of nutrients, thus identify- 

 ing the role of the latter in neurogenesis. 

 Nerve degeneration in thiamine deficiency 

 (beriberi) is a familiar example. Yet, the 

 still obscure "demyelinization" diseases 

 prove that we do not even yet know the 

 requirements of such a common process 

 as myelin formation. Mental derangements 

 have been related to the lack of certain 

 metabolic enzymes (Hoagland, '47), but 

 the effects of metabolic disturbances on the 

 earlier phases of neural development have 

 not yet been adequately explored. There is 

 need for much more systematic investiga- 

 tion. 



The condensed outline of nevurogenesis 

 presented in this article ought to have given 

 some idea of the almost endless array of 

 peculiar conditions of chemical and physical 

 nature called for at every turn of this com- 

 plicated course. To satisfy these ever-chang- 

 ing needs, the milieu presumably under- 

 goes phase-specific changes of composition. 

 In this, non-neural parts or even some other 

 parts of the nervous system may act as pro- 

 viders of the required supplements — in a 

 sense, as sources of specific nutriment. Yet 

 this "symbiotic" interdependence among 

 the tissues is practically unexplored. 



It can readily be seen that the role of 

 hormones, the circularized products of en- 

 docrine glands, is but a special case in this 

 general category of relations. Just a few 

 cursory remarks can be made here on this 

 topic. For convenience, one may distinguish 

 functional from developmental hormone ef- 

 fects, the former modifying the performance 

 of nervous systems that already possess their 

 full complement of neurons, the latter in- 

 fluencing the growth and differentiation of 



