164 



The Nucleus and Cytoplasm in Development 



general concept of genie action in develop- 

 ment is available which gives an intelligible 

 picture of the type of events involved and 

 thus overcomes the apparent contradiction 

 which is expressed in the phrase "in spite 

 of." 



Before discussing this concept it may be 

 pointed out that the assumption of equal 

 genie endowment of all somatic cells cannot 

 be proven rigidly. It rests on the observable 

 equal distribution of the chromosomes, by 

 means of mitosis, to all cells of an embryo 

 and, therefore, presumably on the equal dis- 

 tribution of the constituent genes in the chro- 

 mosomes. It rests, furthermore, on experi- 

 ments on regeneration, particularly in plants, 

 which show that at least some differentiated 

 cells still contain all potentialities to form 

 a whole organism with all types of differen- 

 tiated tissues and organs. These experiments 

 are supplemented by others, in which cleav- 

 age nuclei of early developmental stages 

 have been shown to be totipotent (review in 

 Spemann, '38). None of these results can be 

 taken as actual evidence for an unchanged 

 genie content of differentiated cells. While 

 they seem to disprove schemes involving a 

 kind of mechanical sorting out of genie ele- 

 ments in development which would give one 

 cell one part of the initial total gene assort- 

 ment and another cell a different part, they 

 do not exclude a hypothesis according to 

 which the "same" gene in different cells 

 may possibly become modified in different 

 specific ways. If such a hypothesis were en- 

 tertained it would only be necessary to as- 

 sume that "modifications" of genes are re- 

 versible in cells which, in regeneration or 

 similar experiments, can give rise to new dif- 

 ferentiations. In this sense the hypothetical 

 gene modifications would be basically differ- 

 ent from the gene changes brought about by 

 mutations whose very nature is their perma- 

 nent reproducibility. As will be shown be- 

 low, the hypothesis of genie modification is 

 not required by the facts. It is, however, not 

 inconsistent with them. 



Quantitative differences in the genie con- 

 tent of different cells and tissues have been 

 well established in recent years. The process 

 of endomitosis, by means of which the chro- 

 mosomes of a nucleus multiply without nu- 

 clear division, leads to the presence of poly- 

 ploid constitutions characteristic for various 

 tissues of diverse organisms (for a review and 

 discussion see Huskins, '47). Undoubtedly 

 this polyploidy is part of the differentiation 

 of the tissues concerned but one wonders 

 whether it is more than a concomitant of 



this differentiation. Furthermore, there are 

 many more differentiations than states of 

 ploidy. 



The concept which reconciles the apparent 

 contradiction between essential genetic equal- 

 ity of all cells and their differentiation from 

 one another rests on the existence of regional 

 cytoplasmatic differences in the egg cell and 

 its cellular derivatives. The concept implies 

 a differential response of the genes which 

 during cleavage come to lie in different cyto- 

 plasmic surroundings. The relatively few re- 

 gional differences of the early egg are as- 

 sumed to become increased when cleavage 

 produces new topographic diversity which 

 may lead to physiologic diversity. Each new 

 type of regional diversity sets up a new sys- 

 tem of gene-substrate interaction which ex- 

 presses itself in developmental differentia- 

 tion. For a more detailed discussion of the 

 concept, based on a historical analysis and 

 on new experiments, see Stern ('54). 



The assumed differential response of the 

 genes to the regional extragenic, primarily 

 extranuclear, differences may be thought of 

 in two different but not really mutually ex- 

 clusive ways. On the one hand it is possible 

 that different types of cytoplasm call forth 

 the action of different genes, leaving other 

 genes inactive. If in a region 1 genes A, B, 

 and C find suitable substrates or a suitable 

 milieu, while genes D, E, and F are not pro- 

 vided with suitable conditions for their ac- 

 tion, a differential activity would result in 

 contrast to the situation in a region 2 where 

 A, D, and E might find suitable conditions 

 but not B, C, and F. On the other hand, it is 

 possible that all genes. A, B, C, D, E, F, etc., 

 are active in the cells of all regions but that 

 their reaction products vary quantitatively, 

 as a result of differential kinetic properties in 

 different cells, or qualitatively, by depend- 

 ing on different substrates. This latter as- 

 sumption is compatible with high specificity 

 of genie action if it is kept in mind that such 

 specificity does not need to be restricted to 

 a single substrate but may include a whole 

 class of substrates. 



Such a scheme of differential genie effects 

 in different parts of a developing system is 

 not only a logically consistent derivative 

 from knowledge on the variability of gene 

 effects as dependent on variations in the 

 genetic background and in the environment. 

 Some phenomena are also known where 

 cellular properties can be changed without 

 genie alterations, in a way which may be 

 regarded as a model for developmental dif- 

 ferentiation. Experiments on asexually and 



