278 



Embryogenesis: Progressive Differentiation 



periments with normal living inductors. The 

 elucidation of this problem must wait until 

 more is known about the chemical nature 

 of the inducing agents, of their distribution 

 in the embryo, and of their effects at dif- 

 ferent concentrations. At present, only more 

 or less plausible assumptions can be made. 



Quantitative Aspects. In connection with 

 what will become evident from our later 

 discussion, one may accept the view that 

 differences in the size of the inductive sub- 

 stratum, or in the concentration of the in- 

 ductive agent, can bring about different 

 induction patterns. Thus the formation of a 

 brain, in contrast to that of a spinal cord, 

 is perhaps due in part, though certainly not 

 entirely, to differences in the size of the 

 stimulated area. It is conceivable, fiu-ther- 

 more, that the different components of a 

 synergistic "inductor system" release the 

 same kind of inductive agent and that dif- 

 ferential effects arise from differences in 

 concentration, or in the spatial or temporal 

 application of this agent. The fact that a 

 lens normally arises in contact with the 

 optic vesicle, but that, in the absence of an 

 eye, a lens can be induced by various other 

 tissues of the head (Ikeda, '38) may be 

 ascribed to the existence of a widely extend- 

 ing gradient of the lens-inducing agent. 

 Within this gradient, the optic vesicle would 

 constitute the dominating center which nor- 

 mally prevents the appearance of accessory 

 lenses. This consideration may be applicable 

 to other structures, such as balancer or 

 sucker. 



There is no convincing evidence that 

 quantitative variations of one and the same 

 inductive agent can change its effect-spec- 

 ificity. It is true that progressively heat- 

 inactivated neural inductors induce increas- 

 ingly smaller and less organized formations. 

 Nevertheless, the grafts remain neural in- 

 ductors. This applies also to living induc- 

 tors, such as the medullary plate: when 

 increasingly smaller grafts of this tissue 

 are used, the resulting inductions become 

 smaller and less complex, but no shift to 

 other types of inductions, as for instance 

 mesodermal ones, occurs. When a neuraliz- 

 ing hydrocarbon was applied at different 

 concentrations, the histological type of the 

 inductions remained unchanged (Shen, '39). 



Many attempts have been made to deter- 

 mine in what respect neuralizing grafts dif- 

 fer from lens-inducing grafts, but no defi- 

 nite conclusions could be drawn from these 

 experiments. Pasteels ('40, '45) has inter- 

 preted the successive cephalocaudal dis- 



appearance of entomesodermal tissues in 

 centrifuged or chemically treated embryos 

 by assuming that the treatments produce a 

 progressive lowering of a "morphogenetic 

 potential" or, in other words, a depression 

 of the concentration gradient of "organi- 

 sine." This interpretation, however, still 

 lacks a biochemical foundation. Similarly, at- 

 tempts at ascribing the induction of neural 

 tissue, as against neural crest derivatives, to 

 different concentrations of "organisine" have 

 remained questionable. 



Altogether, it appears unlikely that merely 

 quantitative differences of one type of agent 

 can account for the diversity of the induc- 

 tion phenomena observed. The fact that of 

 the wide range of reaction capabilities only 

 one becomes manifest in a given case seems 

 to indicate that at least some of the inductive 

 stimuli differ from each other qualitatively 

 and that they act selectively upon the array 

 of multiple capabilities (competence). 



Qualitative Aspects. When normal trunk 

 inductor or certain adult tissues are de- 

 vitalized by heat, cold, or drying, they lose 

 abruptly their capacity of inducing meso- 

 dermal structures, but their neuralizing ca- 

 pacity is fully retained, if not increased, 

 and only after prolonged boiling in water, 

 or exposure to temperatures above 100°, 

 does the latter decrease slowly and finally 

 disappear. 



On the other hand, treatment with various 

 fat solvents does not appreciably reduce the 

 mesodermizing but may strongly diminish 

 the neuralizing capacities of adult tissues. 

 Extraction with salt solutions or proteolytic 

 enzymes nearly abolished both capacities. It 

 appears, therefore, that some tissues contain 

 simultaneously several kinds of inducing 

 agents which can be eliminated selectively. 

 On the basis of these and other findings, Holt- 

 freter ('34a), Chuang ('39) and Toivonen 

 ('40) have distinguished between a "neuraliz- 

 ing" and a "mesodermizing" agent. 



In most instances when mesodermal tis- 

 sues arose under the influence of either 

 normal or atypical inductors, they did not 

 appear singly but as an array of different 

 tissues which could exhibit the character- 

 istic pattern of a trunk or tail (Fig. 104). 

 These experiments therefore could not deter- 

 mine whether or not the emergence of the 

 different components of the chorda-meso- 

 derm material is due to the action of differ- 

 ent stimuli. However, the data obtained from 

 the treatment of prospective mesoderm with 

 lithium, urea, or ammonia have shown that 

 some of these chemicals have a specific chor- 



