In this interesting grant proposal, Dr. Abmayr intends to study an aspect of muscle cell formation that is currently poorly understood. Using Drosophila as a model system, she intends to investigate the mechanism by which fusion of myoblasts is controlled and regulated. Muscle cells are one of the few cells that can form multinucleate syncitia. While other aspects of muscle cell differentiation have been studied intensely, little is known about the mechanism of myoblast fusion. Muscle fibers can attain precise sizes in accordance with their location suggesting that there is a highly regulated decision-making process associated with patterning. In Drosophila, there is ample evidence that those decisions are made quite early in myoblast determination. In this proposal, it is intended to take advantage of a combined genetic and molecular approach to examine myoblast fusion. In particular, the cloning of two novel genes called sticks and stones (sns) and myoblast city (mbc) will be attempted. Mutant phenotypes associated with these genes include a dramatic decrease in differentiated muscle fibers and, importantly, a large number of unfused myoblasts. After the cloning of these genes their sequences will be determined, critical protein encoding and promoter regulatory regions will be mapped. In addition, vertebrate homologues will be isolated, expecting that these genes, like many other developmental genes, are highly conserved in evolution. It is therefore possible that this analysis will also lead to the identification of genes that are crucial for vertebrate muscle cell fusion.
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