REGENER\TION IN VERTEBRATES 281 



1959 ) ; for example, buds deprived of an ectodermal covering and then 

 implanted in the coelom develop normally. Fewer assertions have 

 been made about the morphogenetic importance of the apical cap in 

 the amphibian embryo; however, a critical developmental role is 

 ascribed to it and to similar formations in other vertebrates by some 

 workers (Saunders, 1948; Tschumi, 1956; Balinsky, 1956). Balinsky 

 proposes that mesenchymal cells are trapped under the naked epi- 

 thelium, where they interact with it to give rise to the limb rudiment. 



Another sign. which conceivably reflects an importance of the epi- 

 thelium in regrowth of a body part is the fact that during the wound 

 phase and early regenerative stages the epithelium is in immediate 

 contact with wound and regenerate tissues without the intervening 

 barrier of dermal connective tissue or basal membrane that normal 

 skin possesses (see below). However, some observations of Ruben 

 ( 1958 ) suggest that its absence is not absolutely prerequisite for 

 growth. He induced supernumerary formations by implanting frog 

 kidney under the skin of larval Amblystoma limbs. The dermis separat- 

 ing the implant from the epidermis dissolved, but the basal membrane 

 remained while the supernumerary growth was initiated. 



Finally, there is another histological event which signifies, accord- 

 ing to some, an important role of the epidermis in the growth process. 

 Nerve fibers invade the apical cap in great numbers (Singer, 1949, 

 1949a). Since regeneration does not occur without an adequate innerva- 

 tion of the wound area ( see reviews by Rose, 1948; Singer, 1952 ) , the 

 massive and unique invasion of the epithelium may reflect a critical 

 interrelation between nerve and epidermis important for the new 

 growth ( Singer, 1949a, 1952; Thornton, 1954, 1956, 1957 ) . The signifi- 

 cance of the epidermal-nervous relation will be assessed below. 



Although there is agreement that epidermis plays an important 

 role in regeneration of a body part, the nature of the action is not 

 known. A number of theories have been suggested, including direct 

 cellular contribution to the blastema, histolysis, phagocytosis, promo- 

 tion of dedifferentiation, stimulation of regeneration, and maintenance 

 of proper mechanical relations with underlying structures. 



The theory that the epithelium contributes cells to form the under- 

 lying blastema was advanced first by Godlewski for the Axolotl's limb 

 (1928) and affirmed recently by Rose (1948a), Rose, Quastler, and 

 Rose (1955), and Hay (1952) for other urodeles. In Godlewski's view, 

 there is a reserve of indifferent cells located especially in the basal 

 layer of epidermis; they are not definitive epithelial cells but only re- 

 semble them topographically and morphologically. They wander out 

 of the epithelium and lose their resemblance to epidermal cells, de- 

 veloping processes and becoming spindly. Absence of dermis and direct 

 contact of the epidermis with wound tissues serve as a stimulus to the 



