REGENERATION 305 



full agreement on all points. It may be pointed out in the first place that 

 the regeneration process falls into three fairly distinct phases; (i) initiation 

 of the process, and accumulation of a blastema; (ii) growth of the blastema, 

 and (iii) differentiation. These phases can be differentially affected by 

 various means. For instance, Lehmann and Bretscher (1952) found that 

 certain amino-ketones inhibit the first phase (as does x-raying), while 

 colchicine affects mainly the second, and quinoxaline derivatives the 

 third. 



The most important aspect of the initiation process is the production of 

 the apparently undifferentiated cells which make up the blastema. This 

 is usually a response to the injury involved in the amputation, but it can 

 sometimes be brought about by means other than wounding. For instance, 

 a number of Russian authors, beginning with Nassonov, have claimed 

 that the formation of supernumerary limbs (by processes which can be 

 considered as equivalent to regeneration) can be stimulated by injecting 

 various tissue extracts and autolysates into otherwise uninjured axolotls, 

 cartilage extracts being particularly effective (see Fedorov 1946). It seems 

 likely that similar substances, released from the injured cells at the surface 

 of the wound, are important in initiating blastema formation in the 

 normal case. In adult Anura, under ordinary circumstances regeneration 

 is either very sHght or does not occur at all; and this seems to be due to an 

 incapacity of the animal to produce a blastema. If a wound surface in such 

 an animal is treated with strong sodium chloride solution (Rose 1944) or 

 is lacerated mechanically (Polezhayev 1946), blastema cells appear and a 

 considerable amount of regeneration may occur. Denervation of a limb 

 in the urodele amphibian, on the other hand, usually leads to a failure of 

 blastema formation and thus of regeneration {c£. Rose 1948^). 



The next question to consider is whether the blastema cells in verte- 

 brates are derived from reserve undifferentiated cells or from the dediffer- 

 entiation of the tissues in the near neighbourhood of the wound. Experi- 

 ment has now demonstrated that the second of these is by far the most 

 important source of the regenerating cells, although a minor contribution 

 may come from the relatively undifferentiated connective tissues near the 

 cut. The local origin of the cells can be demonstrated as follows: A hmb 

 is removed from a normal diploid urodele and a similar limb from a 

 haploid specimen of the same species is grafted into its place. After union 

 is complete the limb is amputated again, leaving only a smaU segment of 

 the haploid limb attached to the stump. The regenerated limb is then 

 found to be haploid and must have been derived from the cells of the small 

 haploid segment (Hertwig 1927). Again it is a very general observation 

 that irradiation with x-rays decreases an animal's capacity to regenerate 



