CELLULAR DIFFERENTIATION AND EXTERNAL ENVIRONMENT 



73 



apical regions, but if returned to flowing, 

 well-aerated water, the stolon tips become 

 hydranths. Similarly, cut pieces with all 

 hydranths removed develop only stolons in 

 standing water, but reconstitute hydranths 

 and stems in flowing aerated water. Here 

 what we may call the physiological level 

 (determined by difference in oxygen 

 supply) determines different lines of dif- 

 ferentiation — with low oxygen, the stolon 

 with persistent growing tip, and with high 

 oxygen, the rapidly differentiating hy- 

 dranth with sensorimotor reactivity. In 

 other species, less susceptible to low oxy- 

 gen, stolon development in place of hy- 

 dranths can be induced by various depress- 

 ing agents, cyanide, anesthetics, etc., and 

 transformation of stolons into hydranth- 

 stem axes by return to water. 



A striking characteristic of axiate pat- 

 tern in the earlier stages of development, 

 and in many of the simpler organisms 

 throughout life, is a quantitatively differ- 

 ential susceptibility of cells at different 

 levels to a large number of chemical and 

 physical agents. This susceptibility is to 

 a high degree non-specific for certain 

 ranges of concentration or intensity of 

 different agents; that is, susceptibility de- 

 creases in the same direction with the dif- 

 ferent agents. In general, the higher 

 levels of a gradient pattern, that is, those 

 characterized by greater developmental 

 activity, higher rate of respiration, dye 

 reduction, etc., are most susceptible to in- 

 hibiting, toxic, or gradually lethal concen- 

 trations or intensities. This has been 

 found to hold for various organisms with 

 anesthetics, cyanides, various salts, strong 

 and weak bases and acids, several alkaloids, 

 vital dyes, increased and decreased osmotic 

 pressure of aqueous medium, visible light 

 with photosensitization by eosin, ultra- 

 violet. X-rays, radium, extreme tempera- 

 tures, lack of oxygen, and in a few cases 

 supersonic vibrations. Obviously the agents 

 do not all act on living protoplasms in the 

 same way; they do not all inhibit respira- 

 tion or oxidations directly. How then is 

 the absence of specific regional effects to be 

 accounted for? The interpretation which 



suggests itself is briefly this: the axial dif- 

 ferences on which differential susceptibil- 

 ity depends are predominantly or wholly 

 quantitative gradients; granting this, we 

 may expect that any interference with or 

 disturbance of such a system by an ex- 

 ternal action above a certain threshold, but 

 not immediately destructive of the whole, 

 affecting any essential component or ac- 

 tivity, will result in a gradient of effect 

 corresponding in general to the gradient 

 of rate of change constituting the life of 

 the system. Such interference with living 

 protoplasmic systems usually results in 

 toxic effect, retardation or complete inhi- 

 bition of development, and if extreme, in 

 death. With proper experimental proce- 

 dure all these effects give evidence of dif- 

 ferential susceptibility. This axial differ- 

 ential in effect of external agents makes 

 possible differential modifications of form 

 and proportions in development and al- 

 teration of the course of differentiation and 

 the developmental fates of cells. 



In differential inhibition of development 

 the higher levels of gradient pattern are 

 most inhibited. In a simple apicobasal or 

 anteroposterior gradient apical or anterior 

 regions are most inhibited, basal or pos- 

 terior least. The most inhibited regions 

 are not only relatively small in size, but 

 their differentiation is also inhibited more 

 than that of less susceptible regions, and 

 differentiation which normally occurs in a 

 certain region may be shifted to another, 

 but in general results are to a high degree 

 definite, orderly and reproducible. In the 

 echinoderm embryo, entoderm develops 

 from the lower levels of the primary grad- 

 ient, ectoderm from the upper levels. 

 "With differential inhibition, cells which 

 would normally be ectodermal become en- 

 toderm; even the whole prospective ecto- 

 derm may become entoderm with sufficient 

 depression or inhibition. 



Developmental evidence of axiate pat- 

 tern can be decreased and even completely 

 obliterated by leveling down the gradient 

 concerned through differential inhibition. 

 The ventrodorsal or dorsiventral pattern is 

 usually obliterated with less extreme inhi- 



