It is clear from work in Caenorhabditis elegans, Drosophila and vertebrates that LIM homeobox (Lhx) genes play pivotal roles in neuronal differentiation. The overall goal of this proposal is to gain insight into the function of Lhx genes using a genetic screen designed to identify targets of the lim-6 transcription factor in C. elegans. The experimental design makes use of the experimental advantages of C.elegans that include genetic amenability, its well-characterized nervous system, and its completed genome sequence. These studies are likely to dissect genes required for function of a defined GABAergic neuronal circuit as well as illuminate the process of neurite sprouting. A complete elucidation of the molecular events underlying neurite sprouting has great promise to provide an understanding of how Lhx genes are linked to this process. It is also worthwhile to note that understanding the molecular basis of neurite sprouting is an important goal given its occurrence in several pathological states such as Alzheimer's disease, epilepsy, and other neurodegenerative conditions. Thus, this approach is highly likely to uncover details of central importance to understanding neural differentiation.
