During previous funding periods, we have learned that C. elegans uses a conserved system of homeotic genes (HOM-C genes) to generate anteroposterior (A/P) body pattern, and we have investigated the role of this complex in patterning several cell types. We now plan to focus on one biological process that involves the HOM-C genes: cell migration. The Q neuroblasts, QR and QL, are bilateral homologs that migrate in opposite directions. The QL cell migrates posteriorly into the domain of the HOM-C gene mab-5. As it does so, it begins to express mab-5, which functions within its descendants to cause them to migrate to posterior rather than anterior positions. QR instead migrates anteriorly into the domain of the HOM-C gene lin-39, which, in turn, allows the descendants of QR to migrate to specific anterior positions. Together the cells in the Q lineage migrate to positions that span the entire A/P body axis. Our findings suggest that, once programmed by the homeotic genes, the cells find their positions using a global system of guidance cues. We have identified genes required for specific steps in Q cell migration. These include (i) a gene required for left/right asymmetry, (ii) genes required to switch on mab-5 in the migrating QL cell, (iii) a candidate for a migration gene regulated by mab-5 (iv) a gene that may be part of a system of positional information that guides the cells; (iv) a gene required for certain cells to stop migrating, and (v) genes that probably function in the mechanics of migration itself. The mechanism of Q cell migration is probably evolutionarily conserved because it involves integrin receptors, which mediate migration in vertebrates. During this funding period, we will identify additional genes that affect Q cell migration, and we will carry out experiments with these and previously identified genes that are aimed at learning what signals trigger HOM-C gene expression in migrating cells, how the HOM-C genes program the cell's migratory behaviors, and what types of extracellular cues guide these cells to their destinations.
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