We are interested in how the embryonic morphogenesis of the head hypodermis is regulated. Mutations in the C. elegans Pax-6 homolog
vab-3 cause distinctive variable 'Notched head' phenotypes, in which morphogenesis of the ventral anterior hypodermis is abnormal. We have begun an analysis of other loci that mutate to similar Notched head phenotypes, reasoning that these genes might function in the Pax-6 pathway or in parallel pathways regulating anterior hypodermal morphogenesis. Mutations in
vab-1 II and
vab-2 IV have been identified by several workers based on their Notched head phenotype.
vab-1 is defined by ten alleles, including the three highly penetrant alleles
e2027,
dx14 and
dx31 (thanks to Eric Lambie for his UV-induced alleles). In addition to their Notched head phenotype these strong alleles cause abnormal hypodermal morphogenesis in the body and tail, leading to embryonic or larval lethality. 40% of
vab-1(
e2027) broods arrest during embryogenesis, with the earliest arrest stage soon after morphogenesis begins. In such embryos the hypodermis appears to fail to enclose the embryo.
vab-2 is defined by six mutant alleles of variable penetrance. In addition to their morphogenetic defects, which are similar although generally less penetrant than those of
vab-1, some
vab-2 adults are strongly egg-laying defective. The basis for this Egl phenotype, which is seen in all
vab-2 alleles, is being investigated. Since
vab-1 and
vab-2 are the two loci most commonly mutated to Notch-head phenotypes these genes may play specific roles in head hypodermal morphogenesis. Alternatively, the widespread defects in hypodermal morphogenesis in strong
vab-1 and
vab-2 mutants may reflect a general requirement for the function of these genes in hypodermal development, in which case head morphogenesis might be more sensitive to reduction in
vab-1 or
vab-2 function. To determine whether
vab-1 and
vab-2 function in a genetic pathway with
vab-3 we are examining
vab-3 expression in
vab-1 and
vab-2 mutants. Preliminary evidence indicates that expression of VAB-3 protein is at least initially normal, suggesting that
vab-1 and
vab-2 could act either downstream or in parallel with
vab-3 in regulating head morphogenesis. Further genetic mapping of
vab-1 and
vab-2 is in progress, with the aim of cloning these genes.