IV REGULATING FACTORS OF THE PFS 52 1 



manders in response to the removal of the lens from the eye has been given con- 

 tinued consideration by Stone (1955) and by Reyer (1954) (Reyer and Stone, 

 1955). These systems may prove to be advantageous since they provide tissues at 

 more advanced stages of development and are more easily accessible to the neces- 

 sary manipulations in the exploration of inductive mechanisms. 



In pursuing the cjuestion of the chemical nature of the factors responsible for the 

 apparent qualitative changes of the protein forming system Brachet has repeatedly 

 stressed the possible importance of RNA as a controlling factor. A summary by 

 Brachet of the formidable body of suggestive observations is found in another 

 chapter of this volume. Recently Yamada and Takata (1956) and Hayashi (1956) 

 demonstrated morphogenetic effects of nucleoproteins obtained from the liver and 

 the kidney. It should be pointed out, however, that some RNA proteins lose 

 their activity after tryptic digestion and remain active after treatment with RNase 

 (Yamada and Takata, 1955; Hayashi, 1955) suggesting that it may be the pro- 

 tein component which is responsible for the inducing activity. 



Leads as to the nature of the mesodermal activating factors can be found in the 

 work of Niu and Twitty (1953) and Niu (1956) and in the experiments by Toivo- 

 nen (1950, 1952) and Toivonen and Saxen (1955) which demonstrate a mesoder- 

 mal induction with bone marrow extracts. As Nieuwkoop (1955 p. 270-271), 

 points out, the action itself (of the principle obtained from bone marrow) may not 

 be the same as the physiological "transforming principle" of the mesoderm. 

 However, the use of the bone marrow principle may be advantageous in studying 

 the process of transformation itself (Yamada, 1958). 



For a long time, changes in the metabolic patterns of the developing cells have 

 been regarded as important factors in the regulation of developmental process. 

 Various gradient theories, referring to gradients of basic metabolic activities 

 such as oxidation-reduction processes (Gustafson, 1954; Horstadius, 1953, 1955; 

 Lindahl, 1942; Pease, 1941; 1942a and 1942b), were considered to control the 

 development of the animal and vegetal structures of the sea urchin embryo and of 

 characteristic products of diflferentiation in many other lower organisms. Meta- 

 bolic intermediates resulting from the oxidative degradation of glucose phosphate 

 were found to promote development of ectodermal structures (animalization) 

 (Horstadius and Gustafson, 1948 and Horstadius, 1949). 



An interesting transformation in vitro of squamous, keratinizing epithelium into 

 cuboidal mucus-producing epithelium depending upon the vitamin A content of 

 the medium has been observed by Fell (1953) and Fell and Mellanby (1953), 

 and by Weiss and James (1955). Although a metabolic role of vitamin A has not 

 been established the results of experiments by Ernster et al. (1950) on the role of 

 vitamin A as coenzyme, may justify the inclusion of a vitamin A effect ainong in- 

 stances of metabolic control of differentiation. 



A transformation in vitro of the chorion epithelium into keratinizing cells was 

 observed by Moscona (1958). 



Intercellular metabolic reactions (Herrmann and Hickman, 1948b) and their 

 possible role in differentiation of more complex tissues (Flexner, 1939; Flexner 

 and Stiehler, 1938) have been discussed in a previous review (Herrmann, 1952). 



Exactly how, qualitative or quantitative, differences in energy metabolism can 



Literature p. sjg 



