532 



MOLECULAR MECHANISMS OF DIFFERENTIATION 



thetic process than the microsome bound RNA, since fractionation of RNA may be 

 facihtated in this free state. 



In view of the great interest of the embryologists in the mechanisms of differentia- 

 tion by the interaction of embryonic cells, experimentally induced protein for- 

 mation in microbial organisms has become a model system of great significance 

 for the study of inductive processes. A possible relationship between enzyme 

 induction in unicellular organisms and embryonic differentiation was anticipated 

 by microbiologists about ten years ago (Monod, 1947; Spiegelman, 1948). Experi- 

 mental advances made since then are discussed by Monod and by Colin in contri- 

 butions to a symposium on "The Origin of Enzymes." Together with papers by 

 Ephrussi (Enzymes in cellular differentiation), Gale (Nucleic acids and enzyme 

 synthesis), and Spiegelman (On the nature of the enzyme forming system) and the 

 penetrating discussions following these papers, this symposium (Gaebler, ed. 1956) 

 can be expected to open numerous approaches to a fundamental analysis of em- 

 bryonic cells. Studies of the kinetics of enzyme induction in bacteria and of its 

 inhibition indicate that this process is the result of an interaction of inducing sub- 

 stances with some presumably large molecular cell component of the protein 

 forming system, which in a modified form catalyzes synthesis of an apparently new 

 protein type. Such inducing mechanisms were postulated by Cohn and Monod 

 (1953) for the induction of the enzyme galactosidase in E. coli and by Pollock 

 (1953) for the formation of the enzyme penicillinase, which catalyzes the break- 

 down of penicillin in Bacillus cereiis. In the latter case it was found that contact of 

 the bacterial cell with penicillin for one minute was sufficient to induce enzyme 

 formation when the bacillus was grown after this period in penicillin-free medium. 

 It should be emphasized that this is an instance where an induced enzyme persists 

 even after removal of the inducer. Tests with ^^S labelled penicillin showed that 

 an amount of about 100 molecules of penicillin per cell suffices for penicillinase 

 production to proceed at maximum speed. The discrepancy in the quantities of 

 inducer needed and enzyme produced suggested that the penicillin reacted with or 

 acted upon a catalyst which is involved in the synthesis of the enzyme. Again the 

 assumption was made that the production of new enzyme (penicillinase) is initiated 

 by a modification of a part of the PFS by the inducer. From the results of their 

 experiments Monod (1956) and Cohn (1956) conclude that induction of an enzyme 

 like beta-galactosidase in Escherichia coli involves a transient exposure of the cell 

 to the inducing substance at a concentration sufficient for the formation of a system 

 that concentrates the inducing chemical {e.g., galactoside) in the bacterial cell and 

 leads subsequently to formation of an adaptive enzyme. Once formed, the concen- 

 trating system persists even in the presence of a minimal concentration of the 

 inducer which would not be sufficient to induce either the concentrating mechanism 

 or the adaptive enzyme. In many instances embryonic induction depends on at 

 least transient close proximity of the inducing and the responding tissues. It may 

 be that during this short period the inducing material reaches a concentration 

 threshold in the vicinity of the responding cell which is sufficient for the establish- 

 ment of a concentrating mechanism. With the subsequent accumulation of the 

 inducing material (it may be a multiplicity of chemical entities) in the cell, 

 formation of new types of proteins would be elicited. After the transient interac- 



