Experiments on skeletal growth and development in vitro in relation to the problem of avian phokomelia

Abstract

The experiments to be reported in the following pages were suggested by observations made by one of us on the so-called Creeper fowl. Creeper chickens are characterized by a disproportionate shortness of the long bones of the extremities. Histological study has shown that Creeper chickens belong in the same category as the disproportionate dwarfism of mammals known as chondrodystrophy or achondroplasia (Landauer, 1931) . The Creeper characters are inherited as a Mendelian dominant and are lethal in homozygous condition (Landauer and Dunn, 1930). Homozygous Creeper embryos generally die after about 72 hours of incubation, but in rare cases they survive beyond this stage and continue development up to nearly hatching time. These late stages of homozygous Creeper embryos exhibit striking malformations of the extremities which are known as phokomelia (Landauer, 1933). A study of the early embryonic development of homozygous Creeper embryos (Landauer, 1932) led to the conclusion that the effects of the Creeper mutation are not brought about by specific gene action on those body parts which later show deformities, but by a general retardation of body growth at a definite stage of development. This conclusion was strengthened by a detailed comparison of embryonic and post-natal bone growth in heterozygous Creeper and normal chickens (Landauer, 1934). All evidence which so far has been obtained in this work points to the conclusion that the characteristic traits of heterozygous as well as homozygous Creeper chicks are produced by an unspecific retardation of development at a time when formation of the buds of the extremities (and of the head which in homozygous embryos also shows deformities later on) are proceeding at a particularly rapid rate, thereby causing specific disturbances in the differentiation of these parts. It seemed to us that it should be possible to put these conclusions to an experimental test. The most promising way of approach appeared to be an attempt to produce in vitro the extreme abnormalities of bone formation shown by the extremities of phokomelic homozygous Creeper embryos. These abnormalities chiefly consist in (1) a general retardation of cartilage differentiation; (2) lack of bone formation; and (3) frequent partial fusion of ulna and radius on the one hand, tibia and fibula on the other, or presence of only one bone in these segments instead of two.