S2 



CHAPTER 6 



ago; when both parents arc chondrodys- 



trophic, some children are phocomelic and 



have severelj deformed limbs. The condi- 

 tion observed in such individuals can be at- 



tributed to the presence of a mutant gene 

 (like the Cp gene in fowl) in a double dose, 

 that is. when homozygous. 



It was already mentioned that at 36 hours 

 of incubation. Cp - individuals develop 

 more slowlj than -f + individuals. In nor- 

 mals at this stage the tissue for the hind 

 limb buds grows very rapidly, whereas other 

 tissues grow more slowly. If some of the 

 effect of Cp in single or double dose is to 

 cause a generalized slowing-down of growth, 

 the structures most affected will be those 

 growing most rapidly at the time. Such a 

 genetically-induced slowdown in growth rate, 

 starting at about this particular time in de- 

 velopment, is expected, therefore, to reduce 

 the size of the hind limbs and the long bones 

 of fore limbs. 



It should not be concluded, however, that 

 the tissue for hind limb is completely passive 

 to Cp action and that its sole response is the 

 slowdown in growth rate. We can study 

 the developmental fate of prospective hind- 

 limb tissue by transplantation experiments. 

 If such tissue from a normal chick embryo 

 is transplanted to a more forward position 

 in another normal chick embryo, it grows 

 out as a normal limb. If, however, the pro- 

 spective hind-limb tissue from a homozygous 

 Creeper embryo is transplanted to a more 

 forward position in a normal chick embryo, 

 it grows out as a Creeper type leg. This 

 result demonstrates that even at a very early 

 stage, before there is any actual hind limb, 

 prospective limb tissue from Creeper is 

 already permanently determined by the 

 Creeper genotype to develop as Creeper 

 limb, that is. its competence to develop nor- 

 mally is already lost. 



It also should not be assumed that all ab- 

 normal tissues found in homozygous Creep- 

 ers have been determined at an early stage 



in development and, thus, possess only the 

 Creeper alternative. As mentioned, CpCp 

 individuals have small, split eyes. The earl) 

 eye anlage [imaginal disc) from a normal 

 embryo can be transplanted to an abnormal 

 position in a normal embryo. In this posi- 

 tion it grows into an eye just like that of 

 homozygous Creeper, but an eye anlage from 

 a Cp Cp embryo, transplanted to the eye- 

 forming region of a normal embryo, grows 

 into a normal eye. We can conclude, there- 

 fore, that the abnormal Creeper eye is due, 

 not to some change in the competence of 

 the eye tissue, but rather to some kind of 

 abnormality in its surroundings. It can, 

 therefore, be supposed that in the Creeper 

 homozygote the normally competent eye 

 anlage probably undergoes a kind of starva- 

 tion due to the poor circulation that the 

 genotype produces. Such a hypothesis is 

 supported by two lines of evidence: first, 

 most prospective tissues of Cp Cp placed on 

 a complete culture medium /'// vitro grow 

 quite normally, although heart tissue does 

 not grow as well as normal heart tissue; 

 second, when limb rudiments from normal 

 embryos are grown in vitro in a nutritionally 

 dilute culture medium, they develop many 

 of the characteristics of the Cp Cp limbs. 



The study of Creeper fowl demonstrates 

 that the multiple effects of this mutant which 

 have been found at the completion of de- 

 velopment are due to gene-directed changes 

 originating much earlier in development. 

 In fact, we can infer from the developmental 

 fate of prospective limbs in Creeper embryos 

 that a genotype produces changes that pre- 

 cede morphological changes. The Creeper 

 gene apparently modifies the physiology of 

 the individual in such a way that general 

 growth is slowed down, and the prospective 

 fate of certain tissues is fixed, so that the 

 morphological changes later noted are a di- 

 rect consequence of these changes. The 

 gene-caused physiological changes can be 

 attributed, in turn, to changes in the bio- 



