Our overall goal is to define and characterize genes that are required for defined neurons to attain characteristics that allow them to function in dedicated neural circuits. Work from several laboratories including our own laboratory has identified LIM homeobox (Lhx) genes as transcriptional regulatory factors required for individual neurons to function correctly in defined neural circuits.
Our aim i s to deepen our understanding of the function of Lhx genes in C.elegans, which given the significant degree of structural conservation across phylogeny, can be expected to reveal basic mechanisms of Lhx gene function and brain patterning in different organisms. Our research application focuses on the study of a single Lhx gene, lim-6, which is required for a defined motor neuron, DVB, to function appropriately. There are two specific aims: First, we will attempt to describe the anatomical defects associated with loss of lim-6 function, using a variety of markers that will allow us to visualize certain aspects of DVB motor neuron structure. Second, we describe genetic approaches to identify molecular components that may act together with lim-6 to affect DVB motor neuron development; this approach may lead to the identification of long-sought target genes of Lhx proteins. The data obtained so far suggest that lim-6 affects a specific, but as yet unknown aspect of terminal differentiation of motor neuron development. Potential scenarios that could be envisioned are that lim-6 regulates the steps of neuron-target recognition or of neuron-target communication. These studies may give important insights into the function of the vertebrate homologs of lim-6 as well and may reveal common themes of Lhx gene action.
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