280 CELLS, TISSUES, AND ORGANISMS 



wound tissues is intense, the thickening reaches a maximum. The num- 

 ber of layers decreases during subsequent phases of growth and diflFer- 

 entiation. Naville ( 1924 ) was one of the first to remark upon the thick- 

 ening and called it an epithelial cap forming a hypertrophied neoplasm. 

 Faber (1960) speaks of an epithelial lobe for the Axolotl limb regen- 

 erate, which he distinguishes from an epithelial cap in time of appear- 

 ance, in structure, and in persistence. 



The thickened epidermis of the regenerate has attracted consider- 

 able comment recently, first in the work of Thornton (1954), who 

 emphasized that the apical cap, as he terms it, is always present during 

 the formative phases of regeneration and therefore may be prerequisite 

 for the development of the regenerate and may reflect an important 

 action of the epithelium in the new formation. Thornton pointed out 

 ( 1956 ) that, in a stage of tadpole development in which regenerative 

 powers of the limb are lost, an apical cap does not form, whereas in 

 the earlier tadpole capable of regenerating it always appears. He also 

 found that repeated removal of the apical cap prevented limb regen- 

 eration (1957), as did suppression of apical cap formation by daily 

 irradiation with ultraviolet Hght (1958). In the case of Amblijstoma 

 punctatum, however, successive daily removals failed to interrupt limb 

 regeneration, because, according to Thornton ( 1957 ) , of a much faster 

 regeneration of the apical cap in this species— four to five hours. 



There are instances where an apical cap is present but no regen- 

 eration occurs. An apical cap does appear in tadpoles just at the time 

 when they are losing their regenerative powers (Thornton, 1956). A 

 greatly thickened epidermis is observed in the salamander after devia- 

 tion of the brachial artery and its associated sympathetic nerves to an- 

 other wound site than the limb ( Taban, 1955 ) , and yet no regeneration 

 ensues. In irradiated, non-regenerating limbs of the Axolotl an ab- 

 normally thick epidermal cap develops over the wound (Trampusch, 

 1959). We have seen a thickened wound epithelium over the amputa- 

 tion stump of the adult newt in cases in which the limb was pro- 

 vided with a pure motor nerve supply, itself inadequate to evoke 

 regeneration. 



The distal epithelium also thickens during embryonic development 

 of the limb bud in the amphibian and the bird; in the latter case it ap- 

 pears as a ridge over the end of the bud which is called the apical bud 

 or ridge (Saunders, 1948). Morphogenetic importance has been at- 

 tached by some to the apical ridge of birds ( see Zwilling, 1956; Saun- 

 ders, Gasseling, and Gfeller, 1958; Saunders, Gasseling, and Cairns, 

 1959) because after this ridge is removed, the limb or its distal parts 

 fail to develop, even though the wound surface is covered rapidly by 

 adjacent epithelium. Others have denied such a role to embryonic epi- 

 thelium (Amprino and Camosso, 1955; Bell, Kaighn, and Fessenden, 



