534 MOLECULAR MECHANISMS OF DIFFERENTIATION 5 



Myosin formation in the cells of the other primordia is eliminated. In other 

 instances there is no evidence that the cell specific proteins are formed in small 

 quantities before induction of the respective organ {e.g. lens) (Ten Gate and Van 

 Dooremaalen, 1950). Although the sensitivity of enzymatic and immunological 

 methods may not be high enough to determine amounts of protein species of only 

 a few hundred individual molecules, still, the possibility cannot be excluded that 

 induction may require the new formation of a component of the PFS which was 

 completely lacking before induction took place. 



One disadvantage of an interpretation of differentiation based purely on quanti- 

 tative differences in protein production may lie in the difficulty of explaining the 

 apparently irreversible nature of the difTerentiation process. If the formation of 

 either a brain or a lens cell would be merely a matter of adjusting rates of for- 

 mation, e.g. of brain or lens proteins, the reversal of this adjustment should be 

 readily possible. Only if accelerated formation of one specialized protein would 

 lead to an irreversible deterioration of the centers for formation of other proteins, 

 the basis of an irreversibility of differentiation would become apparent. Experi- 

 mentally these possibilities would lead to the following testable conditions. Before 

 the onset of differentiation minimal or near minimal quantities of a series of pro- 

 teins could be detected in the same cell type. In a primitive mesenchyme cell there 

 would be small quantities of myosin ATPase, (premuscle condition), slight amounts 

 of enzyme for formation of chondroitinsulfuric acid (prebone condition) and some 

 enzymes specific for the differentiated erythrocyte or kidney tissue cell. With the 

 onset of differentiation each cell should lose all the minimal activities found in the 

 undifTerentiated cell except the one which is specific for the respective organ. A 

 certain ambivalence of protein forming capacity in difTerentiated organs such as 

 lens formation from some amphibian iris cells (Wolffian regeneration) may be due 

 to an incomplete eradication of the lens forming apparatus in these cells. Actually, 

 by careful analysis this capacity can be found in iris cells of a wider variety of 

 species than was previously assumed to be the case (Sato, 1952/54). 



The postulate of the irreversibility of differentiation invites further comments. 

 Its validity has been questioned by Trinkaus (1956) and by Ephrussi (1956), the 

 latter pointing out that all of the evidence that could be arrayed in its support was of 

 a negative nature. At the same time Ephrussi (1956, p. 33) concludes that whether 

 complete irreversibility is assumed or not, the high stability of the states of restricted 

 potentiality poses a problem to which neither the geneticist nor the enzymo- 

 logist concerned with enzyme synthesis can remain indifferent. To account 

 for irreversibility Ephrussi considers nuclear changes such as deformations 

 of the nucleic acid helices, alterations in the intimate structure of chromosomes, 

 changes resembling bacterial modifications introduced by phage, and the possible 

 role of cytoplasmic self-reproducing units such as plasmagenes or kinetosomes 

 (reviewed by Ephrussi, 1953). Interesting experiments of several authors are 

 discussed by Pollock (1953) suggesting that irreversibility of diflferentiation is 

 associated with the loss of cytoplasmic particles as indicated in the production 

 of the "petite" colony variants of yeast induced by acridine compounds and 

 associated with loss of particles involved in the formation of cytochrome oxidase. 



Aspects of microbiology which are possibly more closely related to differentia- 



