CELLULAR DIFFERENTIATION AND EXTERNAL ENVIRONMENT 



75 



or arms are absent and the larva may de- 

 velop as a completely radial form. The 

 inhibition series of the sea urchin arms and 

 the planarian cephalic lobes are closely 

 similar. The starfish larva differs in form, 

 but shows similar apicobasal and ventro- 

 dorsal differential inhibitions. In later 

 larval stages of the starfish the dorsal side 

 of the foregut shows increased rate of dye 

 reduction and increased susceptibility as 

 the foregut extends ventrally to the mouth 

 region. Normally the coelomic pouches 

 develop right and left from the wall of the 

 foregut, but with differential inhibition of 

 the dorsiventral pattern present at this 

 stage the two pouches arise nearer the 

 dorsal mid-line, are more or less fused, a 

 single median dorsal pouch develops, or 

 coelom development and extension ven- 

 trally of the foregut are completely 

 inhibited. 



All of these differential inhibitions, as 

 well as many others, are similarly related 

 to gradient patterns shown by other 

 methods to be present at the develop- 

 mental stages concerned. They all consti- 

 tute continuous graded series of modifica- 

 tions without evidence of specific relation 

 to particular organs ; even those organs are 

 differentially inhibited. No death or loss 

 of cells is involved in these cases. De- 

 crease in development or absence of parts 

 is not due to absence of specific cells but 

 to decrease or obliteration of the gradient 

 pattern by environmental factors. 



There is another very interesting aspect 

 of differential susceptibility. "With certain 

 lower ranges of concentration or intensity 

 of action of inhibiting agents, differential 

 inhibition is of course less extreme and 

 may be followed after a longer or shorter 

 time, even with continued exposure to the 

 agent, by secondary differential modifica- 

 tions of development opposite in direction 

 from the primary differential inhibition. 

 These result from differential tolerance or 

 differential acclimation or conditioning; 

 that is, acquirement of increased toler- 

 ance, and after return to natural envi- 

 ronment similar modifications result from 

 differential recovery. In these secondary 



modifications the regions primarily most 

 inhibited are most tolerant, become accli- 

 mated or conditioned to the agent most 

 rapidly or most completely, or on return 

 to natural environment recover most rap- 

 idly or completely; they may become rela- 

 tively or even absolutely larger than in the 

 normal animal and are relatively over- 

 developed. 



For example, secondary modifications of 

 the planarian head, differentially inhibited 

 to cyclopia, which occur with differential 

 conditioning or recovery, consist in the 

 following: two additional eye spots which 

 are normally localized right and left; the 

 ganglia approach normal; and the median 

 head region often develops into an elong- 

 ated proboscis-like outgrowth with sensori- 

 motor differentiation, something not found 

 in any planarian under natural conditions. 

 With concentrations or intensities of ex- 

 ternal agents lethal in the course of a few 

 minutes to a few hours, death of the plan- 

 arian progresses from the head posteriorly. 

 With certain lower ranges of the same 

 agents animals may live and remain intact 

 for some days or even two or three weeks, 

 but with death finally beginning poster- 

 iorly and progressing anteriorly. In these 

 cases death may cease at a certain body 

 level because regions anterior to this have 

 become conditioned to the agent and con- 

 tinue to live in it indefinitely. Still later 

 a new posterior end may regenerate and 

 remain alive in the same environment that 

 killed the original posterior end. 



Secondary modifications of the sea-urchin 

 larva give forms with relatively enormous 

 oral lobe, small body, and angle between 

 arms increased up to 180 degrees. Rela- 

 tively megacephalic fish embryos and am- 

 phibian tadpoles may be produced in this 

 way. As might be expected, it is the higher 

 levels of the gradients present which are 

 most tolerant, become most rapidly con- 

 ditioned to, or recover most rapidly or 

 most completely from, the inhibiting action 

 of the agents. The degree and rate of 

 conditioning and recovery differ widely 

 with different agents. For example, with 



