DIFFERENTIATION AND PROTEIN SYNTHESIS 111 



or to form small clusters in a cell which retains its products (see 

 later). 



The demand for a particular product of synthesis by other cells, or its 

 repression by cells already in production (Rose, 1952) which may be the 

 factor determining the course of differentiation by stabilizing a pattern of 

 synthesis, is symbolized by the feed-back arrows at A (environment to 

 cytoplasm) and B (cytoplasm outwards). The presence of soluble unused 

 products in the cytoplasm may ultimately suppress the production of the 

 RNA copies required for their formation: used products (i.e. secreted or 

 rendered insoluble or " wrapped up " in the cell) will not provoke this 

 kind of feed-back against themselves. 



Epidermal cells may be freer of this kind of control than other cells (p. 

 146); their characteristic differentiated products seem to be produced 

 because they possess free surfaces which face the environment. The 

 various surface induced responses have been mentioned (p. 37), but it 

 must be admitted we have little idea of how the results are produced. 



We approach firmer ground when the problem of RNA participation in 

 cytoplasmic synthesis is considered. The greater cytological detail made 

 possible by electron microscopy has, on the whole, supported and ex- 

 tended the views of earlier microscopists. 



When thin sectioning for electron microscopy first developed, glandular 

 cells were immediately examined (see Haguenau, 1958, for review). The 

 RNA-containing nucleolus and the basophilic deposits against the nuclear 

 membrane appeared granular, the nuclear membrane itself double- 

 layered. A more important finding was that the basophilic areas of the 

 cytoplasm contained a system of membranes covered with small dense 

 particles of diameter 120-200 A (Plate 10A). Palade (1955) surveyed a 

 large number of cell-types and established the widespread distribution of 

 these particles. Essentially similar findings were reported by Sjostrand and 

 Hanzon (1954) and Bernhard (Bemhard et al, 1951; see also Haguenau, 

 1958). 



Most of the authors referred to above, recognized at once that the system 

 of membranes-plus-particles must be related to protein synthesis and to be 

 the origin of the cell fragments called microsomes. Palade and Siekevitz 

 (1956) gave a clear proof of this by showing that on mechanical disin- 

 tegration of liver cells the membrane system broke down into microsomes 

 known to be rich in RNA and lipid and which consisted of smaller particle- 

 studded vesicles (Plate 10B). They further showed that after removal of 

 much lipid, the remaining material richer in RNA consisted largely of the 

 dense particles. Their participation in protein synthesis has been further 

 demonstrated by Zamecnik et al. (1956) and Simkin (1959) (Simkin and 

 Work, 1958) who showed that the particles were common in preparations 

 which most actively incorporated amino acids (see below). 



