Our goal is to understand the mechanisms underlying pattern formation and morphogenesis in development. We are focusing on head region development in the nematode worm Caenorhabditis elegans. We have found that the gene vab-3 plays a key role in patterning the head region of the worm, and that vab-3 encodes a member of the Pax-6 family of paired domain containing transcriptional regulators. Pax-6 genes function in head and eye development in other species and are mutated in human eye disorders. Thus, C. elegans and vertebrates use similar genes to pattern their cephalic regions.
Our first aim i s to define the roles of the C elegans Pax-6 locus in the specification of the head region. We have found that the C. elegans Pax-6 locus is genetically complex and that it produces multiple protein products. Existing mutations affect subsets of functions of this complex locus. We will isolate mutations that abolish all products from this locus and thus determine the phenotype of null mutations in the C. elegans Pax-6 locus. The small cell number and defined anatomy makes it possible to analyze the requirements for Pax-6 function with a degree of precision not available in other systems.
Our second aim i s to characterize the genetic pathway in which Pax-6 genes function, as this is likely to have been conserved through evolution. We will use genetic screens for mutations that enhance weak vab-3 mutations or that suppress vab-3 gain-of-function mutations, with the aim of identifying genes that are regulated by Pax-6. We will also search for genes regulated by Pax-6 by identifying mRNAs that are differentially expressed between wild type and vab-3 mutants. Other genes in the Pax-6 pathway may mutate to similar phenotypes as vab-3, so we will therefore also analyze genetically other mutants with similar phenotypes to vab-3 mutants. Homologs of novel genes isolated by the above approaches will be sought in other organisms.
Our third aim i s to identify additional genes involved in head region development. We will perform a general screen for mutants with defects in head region development. This approach may identify components of the Pax-6 pathway and may also identify genes functioning in parallel pathways to control head development.
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