5IO MOLECULAR MECHANISMS OF DIFFERENTIATION 5 



Allfrey, Daly and Mirsky (1955), concerning chemical evidence for such a rela- 

 tionship in mature cells, seems of particular interest. In studying the incorporation 

 of amino acids into nuclear, microsomal, and cytoplasmic proteins of the pan- 

 creas, liver, and the kidney, it was found that feeding of previously fasted animals 

 stimulated the incorporation of amino acids not only into the proteins of the cyto- 

 plasm but also into the proteins of the nucleus. The striking effects led the authors 

 to conclude: "The experiments described in this paper show clearly that under 

 certain conditions uptake and retention of '^N by cytoplasmic and chromosomal 

 proteins are correlated. These experiments do not disclose just how the correlation 

 is accomplished. In a general way, however, it may be said that feeding mice 

 brings about changes first of all in the cytoplasm of pancreas, liver and kidney 

 cells and that the changed conditions of the cytoplasm in some way produce a change 

 in the nucleus. Modifications in chromosomal proteins may, therefore, be regarded 

 as a response to an altered cytoplasm. Since it is well known that chromosomes 

 influence activities in the cytoplasm it may be supposed that modifications in 

 chromosomal proteins specially those combined with DNA will affect the way in 

 which the chromosomes influence the cytoplasm. There can be little doubt that we 

 are here dealing in a fragmentary way with interactions between cytoplasm and 

 chromosomes and that the pattern of interaction here considered, the cytoplasm, 

 changed by external conditions, producing modifications in the chromosomes 

 and these modifications reacting upon the cytoplasm — holds for the physiological 

 changes in non-dividing cells and also for the differentiation that occurs in the 

 course of development." From these conclusions it is evident that the investigation 

 of this hypothesis would be of paramount importance for the embryologist. It 

 would give a clue as to how a constant genome could give rise to the manifesta- 

 tions of differentiation under the influence of some cytoplasmic control. 



IV. REGULATING FACTORS OF THE PFS DURING DEVELOPMENT 



It is assumed that, as a general rule, during the earliest phases of development 

 the specific cell products of the difTerentiated cell (lens proteins, collagen, trypsin) 

 are found at most in small quantities, if at all. In some forms of development the 

 potential capacity to form such cell products may be found to be a fixed property 

 of the embryonic cell at the very onset of development (cleavage). In this case 

 the different components of the PFS must be spatially separated and functionally 

 differentiated in the egg or in the early cleavage stages already. In another 

 type of development the cells retain for a longer time a certain flexibility of develop- 

 ment and can respond to different environmental conditions with the formation 

 of different cell products. Later in development this flexibility is lost. Such a 

 distinction is commonplace to embryologists who have called the first form of 

 development mosaic development, the other regulative development. In the latter 

 case the transition from a labile to a stable state has been called determination. 

 It seems important to recall here this distinction because it must be clear that in 

 approaching the problem of the control of the PFS from an embryological point 

 of view, one may or may not be inquiring into two different processes. One group 

 of processes may involve formation and stabilization of the PFS in regulative 



