Developmental Genetics 



265 



less developed, and does not have the head 

 flexure already present in a + + embryo 

 (right). In fact, differences like this can be 

 seen even 12 hours earlier, i.e., at 36 hours 

 of incubation. 



In both the homozygote and heterozygote 

 for Cp, the differentiation of cartilage has 

 been interfered with. The Cp + individual 

 has the disease called chondrodystrophy (or 

 achondroplasia) (see p. 230), the Cp Cp indi- 

 vidual has the cartilage disease called phoko- 

 melia. Both diseases had been recognized 

 more than a hundred years ago as occurring 

 in human families; cases were found in 

 which both parents were chondrodystrophic 

 and some phokomelic children appeared, 

 whose fingers protruded from the shoulders 

 and whose toes came from a deficient hind 

 limb. The condition observed in these latter 

 individuals can be attributed to the presence 

 of a mutant gene (like the Cp gene in fowl) 

 in double dose, that is, when homozygous. 



It was already mentioned that at 36 hours 

 of incubation, Cp + individuals are develop- 

 ing more slowly than + + individuals. Be- 

 ginning about that time, the tissue for the 

 hind limb buds would normally be growing 

 very rapidly, while other tissues were growing 

 more slowly. Let us suppose that some of the 

 effect of Cp in single and double dose is to 

 cause a generalized slowing-down of growth. 

 In this event, the structures most affected by 

 the slowdown would be those growing most 

 rapidly at the time. The observed effects of 

 one or two Cp genes on the hind limbs and 

 on the long bones of both fore and hind limbs 

 follow expectation from a slowdown in 

 growth rate which starts at about this particu- 

 lar time in development. 



It should not be concluded, however, that 

 the tissue for hind limb is completely passive 

 to Cp action, and that its sole response is to 

 slowdown in growth rate. It is possible, by 

 means of transplantation experiments, to 

 study the developmental fate of prospective 

 hind limb tissue. If such tissue from a normal 



chick embryo is transplanted to a more for- 

 ward position in another normal chick em- 

 bryo, it grows out as a normal limb. If, how- 

 ever, the prospective hind limb tissue is taken 

 from a homozygous Creeper embryo and is 

 transplanted to a more forward position in a 

 normal chick embryo, it grows out as a 

 Creeper type leg. This demonstrates that, 

 even at a very early stage, before there is any 

 hind limb as such, presumptive limb tissue 

 from Creeper is already permanently deter- 

 mined by the Creeper genotype to develop as 

 Creeper limb. 



It also should not be presumed that all ab- 

 normal tissues found in homozygous Creepers 

 have been determined at an early stage in 

 development, so that they possess only the 

 Creeper alternative. It was mentioned that 

 Cp Cp individuals have small, split eyes. 

 The early eye anlage (imaginal disc) from a 

 normal embryo can be transplanted to an 

 abnormal position in a normal embryo. In 

 this position it grows into an eye just hke 

 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 may conclude, 

 therefore, that the abnormal Creeper eye is 

 due, not to some intrinsic differentiation fac- 

 tor in eye tissue, but to some kind of abnor- 

 mality in its surroundings. It may be sup- 

 posed that in the Creeper homozygote the 

 eye is probably undergoing a kind of starva- 

 tion due to the bad circulation the genotype 

 produces. This is supported by two lines of 

 evidence. First, most prospective tissues of 

 Cp Cp placed on a complete cuhure medium 

 in vitro grow quite normally, although heart 

 tissue grows less well than normal heart tissue 

 does. Secondly, when limb rudiments from 

 normal embryos are grown in vitro in a nutri- 

 tionally dilute culture medium, they develop 

 many of the characteristics of the Cp Cp 

 Hmbs. 



The study of Creeper fowl demonstrates 

 that the pleiotropic effects of this mutant 



