Migration to the United States - Developmental Genetics

Creeper chickens were a useful model system for studying the relationship between genetics and development because they displayed a variety of phenotypic effects that begin in utero, including limb, head, and eye abnormalities.  In order to isolate the possible genetic and developmental sources of these differences, Hamburger used the transplantation methods he had helped develop for limb bud transplantation experiments in birds with and without the creeper mutation. The creeper mutant was of interest because in the heterozygous state, legs are greatly foreshortened due to retardation of growth during embryogenesis, while in the homozygous state the eye buds also develop a unique and identifiable abnormality before the embryos die around the seventy-two-hour stage. Since a single gene appeared to affect these two very different traits, Hamburger realized the creeper system and the transplantation techniques he had developed might be used to distinguish the ways in which genes affected developmental pathways.

When he transplanted limb- and eye-bud tissue from the heterozygous creeper strain to the flank of an embryo of a normal strain, the transplant developed the mutant phenotype, as expected (Hamburger 1942). But, when he transplanted an eye primordium from a homozygous mutant to the eye region of a normal embryo, a perfectly normal eye developed. This meant that the genes in the eye primordium of a homozygous mutant were completely capable of normal development. Hamburger’s analysis suggested that the effect of the creeper mutation on limb and eye development must be quite different from each other. The effect on limb growth appeared to be direct; that is, the gene must control some process such as mitotic rate of cells that make up the limb tissue, thus retarding growth. On the other hand, the effect of the creeper mutation on eye development must be indirect, altering some secondary process external to the eye development rather than the developmental potential of cells within the eye itself. The outcome of this work indicated that experimental embryology could contribute in at least a small way to an understanding of the ways in which genes function in development. For the future, he felt “the complete story of the mode of gene action must be written jointly by geneticists, embryologists and physiologists” (Hamburger 1942). But this was about as far as his available techniques could take him at the time. Although he never lost interest in developmental genetics, he recognized that he was at a kind of dead-end, and so by the end of World War II he returned to neuroembryology.

The table below summarizes and color codes the topics covered in each lecture for this course from 1946 to 1969.