REGULATION 153 



observations. The actual presence of a gene can be shown only by its 

 function. But when a character fails to show up, unless the character 

 reappears in the offspring of the cell, it is impossible to tell whether the 

 gene had disappeared or whether its expression was blocked. It is not known 

 whether irreversibly differentiated cells have lost certain genetic determin- 

 ants or whether the expression of the corresponding character was made 

 irreversibly impossible. What we need to answer such a question is a way 

 of testing the activity of the genetic material in a non-differentiated cell or 

 in a cell which underwent another type of differentiation. 



It has not been feasible so far to exchange the DNA or the chromosomes 

 of two differentiated cells to see what happens. But nuclear transfer comes 

 closest to it. Spemann (1928) and Seidel (1932) had found that during 

 early cleavage, the nuclei are equipotential : the nucleus of a dorsal blasto- 

 mere can be replaced by a nucleus from the ventral part without affecting 

 embryonic development. Up to a time when the embryo contains about one 

 hundred cells, the nuclei remain equipotential, they are not irreversibly 

 differentiated. But it should be realized that growth and synthesis (except 

 for nuclear material) had not started yet at that time. Briggs and King 

 (1953, 1959) succeeded in replacing the nucleus of frog eggs by nuclei taken 

 from frog embryos at more advanced stages of development. When the 

 nucleus was taken from a blastula or even from an early gastrula, a stage 

 at which protein synthesis just begins, it was able to replace the nucleus of 

 the egg and ensure a complete development of the embryo into a tadpole. 

 Clearly, the nuclei at those stages had retained all their potentialities, they 

 possessed the same genetic information as the nucleus of a fertilized egg. If 

 the nucleus was taken at a slightly later stage, segmentation took place 

 normally but development was blocked during gastrulation, as if this 

 nucleus had lost some of its capacities. More striking still are the serial 

 transplantations in which the nuclei were taken at an early stage from 

 embryos which had themselves originated from nuclear transfer, and whose 

 development had stopped at an early stage. These never permit full develop- 

 ment (King and Briggs, 1956, 1957). 



Similar experiments were made on another amphibian, Xenopus, by 

 Fischberg et al. (1959) who succeeded in obtaining complete development 

 after transferring nuclei taken from somites, i.e. from a region of the embryo 

 which is already clearly differentiated and which will soon form skeletal 

 muscle ; some of the nuclei were still totipotential 9 hr before the somites 

 became contractile. It would seem therefore that these cells which were 

 well advanced on the way of differentiation still possessed all the genes and 

 that their nuclei were still able to accomplish all the functions of an egg 

 nucleus, when returned to the cytoplasm of an egg. At later stages, however, 

 they became unable to ensure development. 



These experiments indicate that some differentiation can take place 



