The long-term objective of this project is to contribute to the understanding of muscle structure and function, with a special emphasis on how the muscle cell develops. The organism of choice for such a study is the nematode Caenorhabditis elegans. Transparency, self-fertilization, and classical genetics make the worm uniquely suited for the isolation and study of muscle mutations. The muscles of C. elegans are very similar to vertebrate muscles, thus knowledge gained in this system may ultimately aid in the treatment of human muscular diseases and injuries. At a more basic level, it is an exceptional system for the analysis of complex developmental processes, such as the assembly of the muscle filament lattice, and as such, this study may contribute general knowledge concerning cell development. Through mutational analysis, a unique gene which affects muscle development has been identified, named unc-45, where unc stands for uncoordinated. It is essential for both muscle function and the overall development of the worm, yet the genetic map indicates that it does not encode any previously identified muscle component. Genetic and microscopic evidence suggest that the unc-45 gene product interacts with myosin to enable proper muscle thick filament assembly. It has also been observed that the unc-45 gene product is present in the oocyte, although the muscle cells do not develop until the 400 cell stage. Whether the gene product is useful during the pre-muscle stages is a question of general interest to developmental biologists. The goal of this project is the cloning of the unc-45 gene, with the intention of using the clone to analyze the gene's function. This analysis will include DNA sequencing, mutant characterization, and examination of the expression pattern of the gene.
