REGENERATION IN VERTEBRATES 305 



subsequently by Taban (1949, 1955), Thornton (1954, 1956), Goss 

 (1956b), and van Stone (1955). Since regeneration of the hmb is de- 

 pendent upon the nerve supply, without which growth cannot occur, 

 the thought was raised originally that the unique epidermal-nerve 

 relation may be of some importance for regeneration (Singer, 1949a, 

 1952). Thornton (1954, 1956, 1957) suggested that the activity of the 

 epidermis during regeneration of the part is initiated and controlled 

 by this unusual ingrowth of fibers. He imphed that the nerve causes 

 the apical thickening which in turn plays a role in the growth. He no- 

 ticed that the apical cap was absent in anuran tadpoles which had 

 recently lost the power to regenerate, and at the same time few fibers 

 were found in the epithelium. A causal relation between nerve fibers 

 and formation of an apical cap was accepted by Goss (1956b), van 

 Stone (1955), and others. Goss (1956b) advanced an elaborate 

 scheme, in his study of fish barbel regeneration, which pictured the 

 nerve as causing the epidermis to grow and therewith to "provide 

 space" for the accumulation of blastema cells. An epidermis which is 

 not stirred to grow mechanically suppresses the enlargement— a theory 

 upon which we have already commented. 



Certain experiments in our laboratories question the significance 

 attributed to the nervous invasion. In some experiments (Sidman 

 and Singer, in press) we observed a condition in which there were 

 few or no fibers in the epidermal cap of the regenerate and yet re- 

 generation proceeded with considerable speed. The forelimb was den- 

 ervated by ablation of the ganglia and associated sensory and motor 

 roots of the brachial nerves; then adequate time was allowed for motor 

 fibers to regenerate into the field occupied formerly by sensory as well 

 as motor fibers. As a consequence, the motor fibers multiplied and 

 supplied the limb with an excess number. The normal motor supply 

 is not adequate in number to evoke regeneration in the complete ab- 

 sence of sensory neurons, but in the case of the hyperplastic motor 

 innervation, regeneration occurs in about 40 per cent of the instances 

 after amputation ( Singer, 1952 ) . Histological examination of these 

 early regenerates seldom showed nerve fibers in the epithelium; in- 

 stead, the fibers were confined to the blastema. 



The fact that the motor fibers avoid the epithelium is interesting 

 in itself. But the important point brought out by this experiment is that 

 the physical presence of nerve fibers within the epithelium is not a 

 prerequisite of regeneration. This does not mean that the nerve does 

 not excite the epithelium. The agent of the nerve action may be a 

 chemical substance, and by this medium the nerve may influence the 

 epithelium without entering it directly. However, it may be that the 

 nerve exerts no special control upon epithelium. Healing of skin 

 wounds and of denervated stumps does not require the presence of 



