V NUCLEIC ACIDS EMBRYONIC DEVELOPMENT SQI 



of the RNA. Confirmation of this conclusion can be found in recent papers from 

 Yamada's laboratory (1955, 1955a, 1955b): they definitely show that, in kidney, 

 trypsin, but not ribonuclease, abolishes the inducing activity, while RNA itself 

 is inactive. 



One can conclude that, in the case oi abnormal inductors, RNA is not necessary 

 for the activity : the sensitivity of these inductors to proteolytic digestion, and the 

 fact that their activity disappears when NHj-groups are blocked with formalin 

 or ketene (Lallier, 1950; Kuusi, 1953; Smith and Schechtman, 1954) strongly 

 suggests that the inducing activity is linked to the proteins rather than to RNA. 



How far conclusions drawn from abnormal organizers, killed tissues for instance, 

 are valid for the normal, living organizer is a very debatable question. There is no 

 doubt that, as shown by Holtfreter (1947), any agent which induces a condition of 

 sublethal cytolysis in the ectoderm promotes its spontaneous neuralization. But 

 we do not know yet whether the sublethal agents and the normal organizer pro- 

 duce the same biochemical changes in the ectoderm. Recent experiments by 

 Holtfreter (1955) indicate that killed tissues liberate substances, which can diffuse 

 through cellophane membranes and perhaps act on the ectoderm as cytolyzing 

 agents; such a diffusibility is quite different from what has been found in the nor- 

 mal inductors whose action is stopped by a cellophane membrane (Brachet, 1 950 ; 

 McKeehan, 1951). 



These findings suggest that, in contrast to what happens in abnormal inductors, 

 normal induction is mediated by large molecular aggregates, perhaps cytoplasmic 

 granules like microsomes and mitochondria. 



Recent work by Niu and Twitty (1953) lends some support to the view that, in 

 the case of the normal organizer, nucleoproteins play indeed an important part : 

 they found that explanted chordomesoderm produces in the medium a neural- 

 izing agent. Niu and Twitty (1953) exclude the possibility that the neuralizing 

 activity is due to mere toxicity, since no signs of sublethal cytolysis can be detect- 

 ed. If ectoderm is cultivated in the medium in which chordomesoderm has been 

 explanted for a few days, it differentiates nerve fibers and pigment cells. An inter- 

 esting hint is that the culture medium shows a strong U.V. absorption typical 

 of nucleic acids. 



A somewhat comparable finding has been reported by Levi-Montalcini and 

 Hamburger (1953): mouse sarcoma contains a diffusible agent that produces 

 hyperplasia of sympathetic ganglia. When this agent is purified, it is found to be 

 entirely concentrated in the microsomes; like other ribonucleoproteins, it is 

 precipitated by streptomycin and it strongly absorbs U.V. (Cohen, Levi-Montal- 

 cini and Hamburger, 1954). 



It is obvious that much more experimental work is needed before we can 

 assess the real place of RNA in morphogenesis. While RNA is certainly not 

 necessary for induction by abnormal inductors, there is a considerable amount of 

 circumstantial evidence for a role of ribonucleoproteins, probably microsomes, in 

 normal induction by the living organizer. 



It is unlikely that it will ever be possible to demonstrate a role of RNA in normal 

 induction by direct experiments, such as treatment of the living organizer with 

 ribonuclease : the author has performed many experiments of that type, but the 



Literature p. sgg 



