508 MOLECULAR MECHANISMS OF DIFFERENTIATION 5 



of protein formation' in the isolated structural elements of the cell (nucleus, mito- 

 chondria and microsomes) and with the dependence of the synthetic process in 

 these structures on the presence of nucleic acids and on the supply of energy in 

 the form of specific metabolic reactions. 



Representing the second approach, electron microscopy has contributed greatly 

 to an appreciation of the organization and the possible interactions of the isolated 

 sites of protein synthesis within the cell. The results of this work must be taken into 

 consideration in any discussion of protein formation in intact cells. The advances 

 in the analysis of the PFS in mature cells are summarized in the following para- 

 graphs as an essential prerequisite for a discussion of measurements and observations 

 obtained thus far with embryonic cells and an orientation of future investigations. 



The results of the investigations on the PFS of diflferentiated cells can be sum- 

 marized at the present time as follows: 



(i) Ribonucleic acid (RNA) is an important component of the PFS. 



(2) In certain instances the rate of protein formation is related to the actual 

 content of cellular RNA. These results were obtained in cells [i.e. liver, pancreas) 

 in which the protein forming system may be regarded as being stabilized with 

 respect to protein formation. In more labile cells during synthesis of new types 

 of proteins the rate of protein formation seems to depend on the rate of synthesis 

 of new RNA molecules rather than on RNA content alone. The possible impli- 

 cations of each of these aspects of RNA metabolism to protein synthesis in a 

 developing system seems evident. In certain phases of embryonic development 

 differentiation may be marked by the appearance of new types of proteins; 

 at other phases a cell type may differentiate by the preferential accumulation of 

 only certain specific proteins and a corresponding change in the dependence on 

 the metabolism of RNA may be expected. For fully developed tissues such a 

 possibility has been pointed out by Mazia and Prescott (1955). 



(3) In differentiated cells RNA is associated with discrete cytoplasmic struc- 

 tures (microsomes, mitochondria) each of which plays a specific role in protein 

 formation. In embryonic cells RNA may exist unassociated with cell particulates 

 (Brachet, 1952). The absence of structural association during development may 

 make this "free" RNA more adaptable in its function as a component of the PFS 

 or it may be indicative of other unknown differences in its function. 



(4) Considerable evidence has been gathered relative to the site of synthesis of 

 the cytoplasmic RNA involved in protein synthesis. If, as one line of evidence 

 suggests (Brachet, 1952; Taylor ^i a/., 1955), cytoplasmic RNA is synthesized in the 

 nucleus, an approach to the role of the gene in development could be envisioned. 

 Moreover, other experiments indicate that protein synthesis in the nucleus is 

 affected by cytoplasm activities (Allfrey, Daly and Mirsky, 1955). These facts and 

 conjectures suggest possible approaches to the intriguing problem of reciprocal 

 effects of the differentiating cytoplasm on an originally equipotent genome. 



^ Protein formation is used as an inclusive term in those instances where no sharp distinction 

 has been made between (i) net synthesis of proteins, (2) protein formation representing one 

 component of protein turnover, (3) exchange of amino acids without total synthesis of 

 protein molecules. 



