PAX-6 proteins are involved in eye and brain development in many organisms. The C. elegans genome has a single canonical
pax-6 locus that encodes paired type homeodomain proteins with or without an additional paired domain. Mutations in
pax-6 result in pleiotropic phenotypes, including abnormal head epidermal morphogenesis (1, 2). We wish to understand the cellular basis of the epidermal morphogenesis phenotypes in
pax-6 mutants. A major question is whether head morphogenesis defects in
pax-6 mutants are epidermal or neural in origin. Genetic mosaic analysis and tissue specific expression experiments are in progress.
pax-6 mutants display a variety of defects in the nervous system. In
pax-6 mutants both pan-neural and some neuronal cell type specific markers are ectopically expressed in cells anterior to the nerve ring, a region normally containing glia-like cells. Glial markers such as
itx-1-GFP, which is expressed in inner and outer labial socket cells, are also ectopically expressed in
pax-6 mutants. Altogether, our data suggest an increase in both neuronal and glial cells in
pax-6 mutants, possibly a result of either failure in cell death or other lineage transformations.
pax-6 mutations have been found to cause aberrant expression of other neuronal markers, such as the CEM marker
pkd-2-GFP (H.T. Schwartz and H.R. Horvitz; P. Grote and B. Conradt, personal communications). We will report on the basis for this misexpression phenotype. To date, a single direct target of
pax-6 has been defined in C. elegans, the sine oculis homeobox gene
ceh-32. We are using microarrays (Affymetrix and Washington University) to identify genes showing differential expression between
pax-6 and wild type embryos. Genes showing consistent down- or up-regulation in
pax-6 relative to wild type are being investigated. We are also using purified GFP-labeled cells to identify tissue specific targets of
pax-6. The C. elegans genome also encodes a member of the eyegone family of
pax-6-related proteins, Y53C12C.1. In Drosophila, eyegone has functions related to
pax-6. We will present our characterization of the expression and function of this locus. 1 Chisholm, A.D., and Horvitz, H.R. (1995) Nature 377, 52-55 2 Cinar, H.N., and Chisholm, A.D. (2004) Genetics 168, 1307-1322