My research goal is to understand how spatial patterns arise within fields of developing cells: to identify the regulatory signals involved, to learn how they are localized, and to learn how they generate cell-specific responses. I am using C. elegans as an experimental system in order to analyze pattern formation at the level of single, identified cells with both genetic and molecular techniques. By analyzing the gene mab-5, I have discovered a control system in C. elegans that is responsible for antero-posterior differences in body pattern after hatching. mab-5 function cell-autonomously in ectodermal, neuronal, and mesodermal lineages located in a single posterior body region. It is required for posterior-specific patterns, including copulatory sensilla and sex muscles, cell fusion, cell death, and also patterns of cell migration. mab-5 appears to function as a regulator: In mab-5 null mutants, many posterior cells adopt anterior-specific fates. Conversely, when mab-5+ is overexpressed, anterior cells can adopt posterior-specific fates. Properties of this system suggest mab-5 is activated within posterior cells by extracellular signals. As a means of addressing the general problem of pattern formation within fields of cells, we will address three questions concerning mab-5: (1) What is the biochemical function of mab-5? (2) How is mab-5 activated in a position-specific fashion? and (3) How does mab-5 activity invoke cell-specific responses? To determine the biochemical function of mab-5 activity and its mode of regulation, we will initiate a long-term molecular analysis by cloning the mab-5 gene, and analyzing patterns of mab-5 RNA expression. To determine whether particular cells produce signals that activate mab-5 in posterior cells, we will effectively remove individual cells using laser microsurgery. We will also pursue observations suggesting that epidermal signals activate mab-5 in the medsoderm. To identify genes that activate or respond to mab-5, we will identify mutations that affect the positional specificity of mab-5 activity or the cell-specific responses to mab-5 activity. By standard genetic analysis, and also molecular approaches using cloned mab-5 DNA sequences, we will begin to determine how these genes are likely to interact with mab-5 and with one another.
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