REGENERATION IN VERTEBRATES 285 



one or two acidophilic nucleoli, and the cytoplasm becomes very 

 basophilic. At first there is no outer cornified layer, as there is in normal 

 skin, but by about the fifth day cornification sets in and progresses 

 rapidly, so that one or a few layers of cornified epidermis are present 

 on the tenth or twelfth day. The cornified layers are often broken and 

 sometimes ragged as groups of cells slough from them. 



Boundaries and spaces between cells of the apical cap, as viewed 

 under the light microscope, appear more frequently than in normal 

 skin, especially among the basal layers. Fraisse (1885), Barfurth 

 (1891), Tornier (1906), Taube (1923), and Naville (1924) remarked 

 upon the apparent loose contact between epidermis cells of the re- 

 generate. Perhaps the loose arrangement of the basal cells is due to the 

 widespread edema of the blastema and adjacent stump that charac- 

 terizes the early regenerate stages. Reflecting the loose arrangement of 

 the cells of the lower layer is the fact that they may be dissociated 

 easily (Singer, Davis, and Scheuing, 1960). When atropine or another 

 drug was infused into the growth, a large blister formed within the 

 regenerate. Fluid accumulated first between the lower epidermal cells, 

 causing them to separate and float free singly or in clusters. The outer 

 cuticular layers resisted the distending fluid but eventually broke. 



We have seen debris of various sorts in the intercellular spaces of 

 the epidermis — for example, pigment granules and other cellular frag- 

 ments including pycnotic nuclei. We have also seen leucocytes or 

 macrophages, which Fraisse ( 1885 ) was among the first to observe in 

 the regenerate as well as the normal epidermis of the amphibian ( see 

 also Mettetal, 1939). Sometimes the intercellular spaces are greatly 

 enlarged and contain a coagulum and cellular deti'itus, as though an 

 epidermal cell or group of cells has perished and is now being cyto- 

 lysed. Taban (1955) depicted a large lacuna of this sort within the 

 epidermis of the salamander, the contents of which included poly- 

 nucleated cells and partially lysed epithelial cells. Naville (1924) 

 described similar cavities in the regenerating epidermis of Rana and 

 discussed the evidence that pycnotic changes occur along with regen- 

 erative ones. He observed considerable chromatolysis and nuclear 

 changes among basal epidermal cells. Fraisse (1885) also reported in- 

 tercellular lacunae filled with a homogeneous coagulant substance. In 

 the regenerate skin of the salamander, Weber noted (1957) that the 

 epidermis is phagocytic in the early days during and following wound 

 closure removing foreign bodies, dead cells, and fragments. He 

 described cysts which occasionally formed intercellularly and which 

 contained erythrocytes and cell particles of various sorts in addition to 

 phagocytes. In supernumerary formations induced by nerve deviation, 

 lacunae filled with debris appeared in the epithelium at the new site of 

 the nerve (Bodemer, 1958). In addition to small lacunae, we also 



