IV REGULATING FACTORS OF THE PFS 525 



In amphibians the relationship of proliferation, measured as an increase of the 

 quantity of DNA, to differentiation, measured as formation of specific enzymes, 

 has been investigated repeatedly. This material has been subjected to a careful 

 re-examination by Lovtrup (1955) who found a rapid increase in the DNA 

 content of the embryo beginning after segmentation and continuing until the onset 

 of the larval stage indicating a considerable proliferative activity during this 

 period. During the first part of the larval period {Ambystoma mexicanum, 12 days, 

 stage 37-40) no increase in the DNA content occurs and therefore cell proliferation 

 would seem to have abated (however, one can not exclude the possibility that 

 cell increase is compensated to some extent by cell degeneration ) . During the phases 

 in which considerable DNA accumulation occurs there is only an increase in Oj 

 uptake, alkaline phosphatase, and amylase activity, and during the later tailbud 

 stage there is an increase in cathepsin activity and RNA content. This RNA in- 

 crease is regarded as being preparatory to the formation of enzymes during the 

 larval period^ 



The period of depressed proliferative activity during the larval period is dis- 

 tinguished by the appearance and rapid accumulation of numerous cytoplasmic 

 enzyme proteins: cholinesterase, adenosinetriphosphatase, cytochrome oxidase, 

 succinic dehydrogenase, acid phosphatase and tripeptidase. Also catalase and 

 dipeptidase show a slight increase. At earlier phases of development, throughout 

 neurulation and the first half of the tailbud stage, none of the investigated enzymes 

 showed an increase. These results may actually indicate a complementary relation- 

 ship of proliferation and differentiation at least during some phases of the develop- 

 ment of certain amphibians. It should be pointed out, however, that Krugelis et al. 

 (1952) do not find a similar break in their DNA curve for amphibian development 

 [A. piinctatum) and further investigation is needed to obtain more conclusive 

 material. 



The relationship of proliferation and differentiation has found further considera- 

 tion in connection with Goldschmidt's theory of gene action. According to this 

 theory, genes control the rates of developmental processes and abnormal forms of 

 development are caused by quantitative changes in the rates of proliferation of 

 the organ primordia. Interesting examples are the developmental abnormalities 

 which are obtained in Drosophila larvae after treatment with such inhibitors of pro- 

 liferation as nitrogen mustard or colchicine. In the wild type last instar larvae it 

 was found that the normal development of arista was altered to a development of 

 aristapedia (Bodenstein and Abdel-Malek, 1949) while in a mutant which nor- 

 mally forms aristapedia treatment with colchicine led to the appearance of arista 



^ The data on RNA accumulation deserve closer examination. With development taking 

 place at 18 °C or 15 °C the increase in RNA is shifted from stage 18-20 to stage 26, respec- 

 tively. It might be expected that further lowering of the temperature to 13 °C would bring 

 the onset of RNA accumulation to stage 30 or 32. This would bring the onset of RNA 

 accumulation close to the beginning of the period of DNA constancy and would 

 emphasize the possibility of a competitive formation of RNA and DNA and of the depend- 

 ent protein forming processes at this phase of development. In this connection it would be of 

 interest to see whether enzyme formation would be dependent upon the change in the 

 onset of RNA accumulation at different temperatures. 



Literature p. sjg 



