REGENERATION 173 



It is practically certain that the cells of this blastema do 

 not, as, e.g., in planarians, originate from a store, somewhere 

 in the body, of cells which have retained embryonic properties, 

 and which migrate towards the wound. In contrast, they arise 

 locally by de-differentiation of the tissues near the wound. 

 The following type of experiment supports this view. The distal 

 part of a limb is replaced by a limb graft from another 

 individual, the cells of which can be distinguished from those 

 of the host, e.g. by their pigmentation, or haploidy. Thereupon, 

 the graft is amputated almost completely, but so that the cut 

 goes through the grafted tissue only. In this case, the cells of 

 the regenerate have in every respect the character of the grafted 

 tissue, even though the normal tissue of the host begins at a 

 short distance from the wound. Furthermore, it has been 

 demonstrated that the formation of the blastema begins even 

 before there is any considerable increase in the number of 

 cell divisions in the neighbourhood of the wound, so that it is 

 clearly not formed by multiplication of cells. It has not yet 

 been ascertained whether its cells originate mainly from the 

 de-differentiating tissue of muscles and skeleton, or from the 

 connective tissue, or whether, on the other hand, they are 

 supplied for the most part by the proliferating epidermis, as 

 was suggested by Rose (1948). 



On the one hand, de-differentiation of the old tissues supplies 

 the cells for the regeneration blastema, but on the other hand 

 the blastema, once it has been formed, seems to bring the 

 process of de-differentiation to a stop. Butler concluded this 

 from experiments in which regeneration was studied after 

 irradiation of the limb with X-rays. After strong irradiation, 

 the power of regeneration had disappeared completely. Am- 

 putation of the limb led to marked de-differentiation of the 

 stump tissues, but no blastema was formed, and de-differ- 

 entiation continued until the whole stump had been resorbed. 

 The same thing happened after the amputation of a limb which 

 had previously been denervated by transection of its nerves 

 (Butler and Schotte, 1941). Apparently the presence of nerves 

 is indispensable for a normal equilibrium between de-differ- 

 entiation and blastema-formation. Singer (1942-49) has shown 



