278 CELLS, TISSUES, AND ORGANISMS 



adult newt ( see also Singer, 1952, 1959; Schmidt, 1958 ) . A few hours 

 after amputation of the arm the epidermis moves over the wound and 

 within a day completely covers it. In the early days the wound area be- 

 comes inflamed and is infiltrated with phagocytes. During the first week 

 and the early part of the second there occurs some dissolution of bone, 

 some histolysis of other tissues, and the formation of a fibrocellular scar 

 under the wound epidermis. The epidermis progressively thickens; by 

 the tenth to the twelfth day it consists of about 15 layers of cells, in 

 contrast to the three or four of normal epidermis. The thickening is 

 maintained during the early formative phases of regeneration; it sub- 

 sides slowly during later stages. The second week after operation is 

 also characterized by dissolution of the scar tissue and increased his- 

 tolysis of the muscle and other old tissue of the wound. Simultaneously 

 there appear mesenchymatous cells, also called cells of regeneration. As 

 they emerge from among the dissolving adult tissues, these embryonic- 

 like cells accumulate under the thickened epithelium. Abundant nerve 

 fibers are present among the cells of the early regenerate. Indeed, 

 sprouts growing from the amputated nerve stumps invade the wound 

 area within two or three days after amputation ( Singer, 1949a ) . They 

 increase in great numbers in the phase of accumulation of the blastema 

 and invade the epidermis as well. 



The mesenchymatous accumulation, the so-called blastema of re- 

 generation, forms a mound after about two weeks which is grossly 

 visible at the end of the stump and which has been called the early re- 

 generate bud. At this stage the end of the stump and the regenerate 

 are swollen with edema fluid. Rapid growth of the blastema occurs dur- 

 ing the next week, due to numerous cellular divisions; the regenerate 

 enlarges to form at first a bulging dome-shaped growth, the medium 

 regenerate bud, and then a conical one, the late regenerate bud. Dur- 

 ing approximately the fourth week, the end of the regenerate becomes 

 flattened to form the rudiment of the future hand, and the proximal 

 part bends to anticipate the future elbow. At about this time diflteren- 

 tiation of the axial skeleton and then of muscle and other tissues is ini- 

 tiated ( for further references and diagrams of these stages see Singer, 

 1952,1959). 



The importance of epidermis 



Experimental and other evidence seems to point to an essential 

 role of the epidermis in the production of the new part, although the 

 contrary view is sometimes expressed that "the epidermis is either pas- 

 sive or an inhibitor of regeneration" (Nicholas, 1955). When normal 

 skin, including as it does dermal connective tissue, is sewn over the fresh 

 amputation surface of the tail (Tornier, 1906; Godlewski, 1928; Jefi- 



