THE ROLE OF RIBONUCLEIC ACID AND SULFHYDRIL GROUPS 249 



a, b). They used a considerable number (more than one hundred) of 

 chemical analogues of purines, pyrimidines, and nucleosides, and they 

 found, as a rule, inhibition of development at a definite stage. This fact 

 suggests the possibility that new enzymatic mechanisms for RNA syn- 

 thesis appear at definite stages of development. 



In chick embryos, inhibitors of RNA synthesis also impair mor- 

 phogenesis. For instance. Fox and Goodman (1953) found that ab- 

 normal synthetic nucleosides, in which ribose was replaced by another 

 sugar (glucose, for instance), inhibit the development of explanted 

 chick embryos. Waddington et al. (1955) found that the regions most 

 sensitive to chemical analogues ( such as benzimidazole or azaguanine ) 

 are precisely those that show the highest incorporation of methionine 

 into proteins. Once more, RNA synthesis, protein synthesis, and mor- 

 phogenesis appear very closely linked in developing eggs. 



Finally, Hisaoka and Hopper ( 1957 ) have been working on zebra 

 fish eggs and have used barbituric acid as a tool for experimentation; 

 they concluded from their studies that there is a link between morpho- 

 genesis and RNA synthesis in fish eggs as well as in those of amphib- 

 ians and of the chick. 



Substances other than purine and pyrimidine analogues have com- 

 parable effects. For instance, two well-known inhibitors of oxidative 

 phosphorylation, dinitrophenol and usnic acid, completely inhibit mor- 

 phogenesis. The inhibition can be largely reversed if the treated eggs 

 are returned to the normal medium; however, abnormalities (such as 

 persistent yolk plug and microcephaly) can often be found in these 

 cases ( Brachet, 1954 ) . Cytochemical ( Brachet, 1954 ) and quantitative 

 ( Steinert, 1953 ) studies clearly have shown that inhibition of develop- 

 ment and RNA synthesis always go hand in hand: when the dinitro- 

 phenol-treated embryos are brought back to normal medium, RNA 

 synthesis is resumed, but only if morphogenesis also is taking place. 



Another interesting group of substances is the steroid hormones 

 ( stilbestrol, oestradiol, testosterone), which have been studied by 

 Tondury (1947), Cagianut (1949), and Rickenbacher (1956). These 

 substances inhibit cleavage or make it abnormal; furthermore, they also 

 modify the normal gradient of RNA distribution. It seems that, because 

 of alterations of the mitotic apparatus during early cleavage, RNA be- 

 comes unevenly distributed in the daughter cells. At later stages, strong 

 abnormalities of development can be found, the most conspicuous being 

 unequal differentiation of the medullary folds, with an asymmetry of 

 the nervous system as a result. It is a very interesting fact, which cer- 

 tainly deserves confirmation, that, according to Cagianut, addition of 

 yeast RNA to the embryos that have been treated with steroid hor- 

 mones definitely improves their differentiation. 



Something should be said about another chemical, which is famous 



