Mutations causing the degeneration of specific nerve cells have been identified in many organisms. Recently, we have identified four dominant mutations that cause the degeneration and death of specific nerve cells in the nematode Caenorhabditis elegans. Three of these mutations, in the gene mec-4, lead to the deaths of all six of the C. elegans touch cells. The fourth mutation, in the gene deg-1, causes the death of different nerve cells. These genes are of interest because of the high selectivity of their expression and because both can be mutated so as to produce cell degeneration. The proposed research will use these and other mutations to study the process of genetically-produced neuronal degeneration in C. elegans and the nature of the mec-4 and deg-1 genes.
The specific aims of the research are: 1. to analyze genetically the mec-4 and deg-1 genes by isolating and characterizing additional alleles of the genes and studying interactions with other genes; 2. to characterize the events that occur during cell degeneration in these mutants using light and electron microscopy; 3. to clone and characterize molecularly the wild-type and mutant mec-4 and deg-1 genes. The health relatedness of this project stems from the nature of the mutations. We cannot tell whether the mec-4 and deg-1 mutations are direct counterparts of specific disease situations in higher organisms. Nonetheless, the study of these mutations, using molecular and transmission genetics and observations on single, identified cells, should highlight cell biological processes underlying inherited degenerative neurological disorders.
