154 THE BIOSYNTHESIS OF PROTEINS 



without irreversible change occurring in the nucleus. The significance of the 

 loss of capacities of the transplanted nuclei taken at later stages is of course 

 much more uncertain, for it is very difficult to establish whether the change 

 is due to differentiation or to damages caused to the nuclei during trans- 

 plantation; the operation becomes indeed more and more difficult as 

 development progresses. It is not certain at present whether the nuclei 

 undergo a differentiation process. 



In giant chromosomes, metabolic processes have been observed which 

 suggest that some differentiation might take place within the chromosomes 

 themselves. Although the pattern of the bands of the giant chromosomes 

 is the same in the different organs in which they are found, very striking 

 metabolic processes occur at specific regions of the chromosomes. Certain 

 typical euchromatic bands, i.e. bands which are supposed to contain men- 

 delian genes, are changed into large bulbs (Breuer and Pavan, 1955). During 

 this process, a very active incorporation of thymidine takes place, indicating 

 localized DNA synthesis (Ficq and Pavan, 1957; Ficq et al, 1958); RNA 

 is also produced at the same locations. It is remarkable that these metabolic 

 processes occur at the level of well-defined bands, and at certain stages of 

 larval development only. This might possibly reflect a process of nuclear 

 differentiation. 



The sequence of events which result in cytoplasmic and eventually 

 nuclear differentiation is unknown. There is clear evidence that the cyto- 

 plasm influences the state of the nucleus, and that both must in some way 

 be adjusted to one another for proper co-operation. Hybrids between two 

 sea urchins Paracentrotiis and Arbacia, or between two frogs, Rana pipiens 

 and Rana sylvatica, or Rana esculenta with R. temporaria are blocked more 

 or less early during development, usually at gastrulation. In these lethal 

 hybrids, the nuclei of many cells are abnormal, they are overloaded with 

 RNA(Brachet, 1944, 1954; Zeller, 1956). 



If the nucleus of the fertilized egg of R. pipiens is transferred into an 

 enucleate unfertilized egg of R. sylvatica, development starts, but it is 

 blocked at the blastula stage. If the nucleus of one of the blastomeres is now 

 transferred back into an enucleate R. pipiens egg, development is blocked 

 at the beginning of gastrulation. This suggests that the nucleus had been 

 irreversibly changed due to its reduplication in a foreign cytoplasm 

 (Moore, 1958, 1959). 



It is therefore quite reasonable to consider that changes in the properties 

 of the nuclei might be the consequence of differences in cytoplasmic pro- 

 perties. But changes in nuclear activity certainly influence cytoplasm. A 

 cumulative effect will thus progressively be observed, and it is easy to 

 visualize that once nucleus and cytoplasm are engaged in such a cascade 

 of changes which determine one another, the resulting evolution of the cell 

 line will rapidly become irreversible. 



