REGENERATION IN VERTEBRATES 303 



mal (Kamrin and Singer, 1959), yield the most extreme reaction, 

 whereas bits of tissue from the same animal (such as spleen, liver, 

 muscle, nerve, ganglia) yield the least. Indeed, in the latter cases the 

 reaction eventually subsides, as though some chemical balance is at- 

 tained between the two, whereas in the former the reaction continues 

 until the body is encapsulated and thrown out. 



It is important to note that in the experimental situation we em- 

 ployed to test the response of the epidermis, the epidermis itself was 

 not damaged. A foreign body was implanted into the regenerate from 

 below by way of the stump tissues. Consequently the gross epidermal 

 reaction does not depend on direct damage, nor does it depend on the 

 epidermis moving at the time to close a fresh wound. Instead, the re- 

 generate epithelium appears to be attuned in a delicate way to the 

 underlying tissue, and the equilibrium between the two is easily dis- 

 turbed. The epidermal response must be initiated in the basal cells 

 first, because one of its surfaces, "unsatisfied" by contact with other epi- 

 dermal cells and without an intact adepidermal membrane, is in direct 

 equilibrium with the underlying ground substance. When the balance 

 is disturbed, the basal cells move toward the exciting agent and initiate 

 therewith a concerted flow of associated epidermal cells. The quality 

 of the cell that enables it to respond so effectively to alterations in the 

 adjacent environment is not known (see the theories of Weiss, 1958). 

 It must be related in part to the absence of a continuous adepidermal 

 and of a basal membrane; in part it may also be due to a heightened 

 sensitivity and reactivity of regenerate epithelium not shared by the 

 normal. 



We cited some morphological evidence of a discharge of secreted 

 epidermal substance, in this case into the ground substances of the 

 blastema. The basal epidermal cells contained cortical extensions 

 whose structure suggested regions of secretory discharge. Although 

 these signs were obvious only the early formative stages of limb re- 

 generation, it may well be that discharge of secreted substances occurs 

 in other stages as well— indeed, even from cells of normal epidermis. 

 Perhaps the epidermis of the early regenerate is only quantitatively 

 more active. 



Assuming that such a contribution does occur, the nature of the 

 secreted substance may be speculated upon. Since the adepidermal 

 membrane forms in close orientation to the undersurface of the epi- 

 dermis, it is possible that the basal secretion influences its formation. 

 The epidermis may contribute the material for the membrane or a sub- 

 stance to pattern the membrane in relation to the undersurface of the 

 epithelium. On the other hand, we have never seen the adepidermal 

 membrane directly beneath the cellular extrusions. And so the secreted 

 substance may prevent the formation of the membrane, and in fact 



