536 MOLECULAR MECHANISMS OF DIFFERENTIATION 5 



elicited experimentally not only with cells and grafted tissues but also with purified 

 proteins as the antigenic material. From the latter studies it was concluded that 

 this phenomenon was based on a modification of the embryonic PFS, possibly 

 without persistence of the antigenic material itself in the embryonic cell (Cinader 

 and Dubert, 1956). The wide ramifications of the elucidation of this problem for an 

 understanding of the control of the PFS are discussed in a stimulating symposium 

 on "Immunological Tolerance" (Medawar et al., 1956). A modification of the 

 PFS by addition of heterologous proteins to tissue cultures has been claimed by 

 Langman (1953a, b). Confirmation of his results would amount to a demonstration 

 in vitro of a cellular reaction closely related to immune tolerance. A wide array of 

 immunological approaches to the problems of differentiation has been summarized 

 by Nace (1955) and Woerdeman (1955). 



Before concluding this discussion it should be pointed out that in many instances 

 the protein molecule does not assume its functional role in the cell as an individual 

 entity but rather in combination with other protein molecules of the same or of 

 a different species or as a part of a complex of proteins, nucleic acids, mucopolysac- 

 charides or lipids. Participating in such a molecular aggregation the protein mole- 

 cule becomes a building block in the formation of those larger structural units 

 which become visible, at least in the electron microscope, as the smallest distinct 

 morphological units. Thus, in contributing to the formation of supramolecular 

 complexes the protein molecule participates directly in morphogenetic phenomena. 

 Some factors involved in the aggregation process of molecules of the same protein 

 species were explored in a morphogenetic model system, consisting of the aggre- 

 gation of dissolved collagen molecules with the subsequent formation of collagen 

 fibers. More recent progress in this investigation has been reported in an exemplary 

 paper by Jerome Gross ( 1 956) . Of importance from the perspective of morpho- 

 genesis are the recent investigations of Nickerson and his associates (Nickerson, 

 1954a) concerning the metabolic control of the state of polymerization of cell-wall 

 proteins. 



The starting point of this series of investigations was the observation that nutri- 

 tional conditions determine whether yeast will grow as a rapidly budding cellular 

 form or as filamentous mycelium without budding. Further analysis showed that 

 the presence of cysteine in the medium maintains budding and eliminates the 

 occurrence of filamentous forms (Nickerson and Mankowski, 1953). The depend- 

 ence of this transformation upon definite metabolic reactions could be established 

 by the analysis of a divisionless yeast mutant in which budding and cell division 

 did not take place but which grew rapidly in a filamentous condition (Nickerson 

 and Chung, 1954). 



Investigations carried out to explain this difference showed that in the parent 

 strain a metal flavoprotein is coupled to an acceptor which initiates cytokinesis, 

 whereas in the mutant this coupling is blocked and substrate generated reducing 

 capacity is diverted to non-specific dye reduction (Nickerson, 1954b). Since 

 cytoplasmic division is maintained and filament formation prevented by the 

 addition of cysteine the possibility of a shift in the reduction of SS to SH groups 

 as a controlling mechanism in cytokinesis and as a receptor for the metal flavo- 

 protein system was postulated. In supporting this Falcone and Nickerson (1956), 



