Although gastrulation requires dynamic regulation of cell adhesion, little is understood about the role of cell-cell adhesion receptors during gastrulation in C. elegans. In C. elegans, the cadherin complex is essential for early embryogenesis and consists of the single classic cadherin HMR-1, the -catenin HMP-2, the -catenin HMP-1, and the
p120 catenin JAC-1. The immunoglobin superfamily member LAD-1/SAX-7, an L1 cell adhesion molecule (L1-CAM) also plays a role in early development. Both HMR-1 and LAD-1 are expressed throughout embryogenesis starting at the two-cell stage (M. Costa, J. Cell Biol. 141, 297-308). In C. elegans,
hmr-1(
zu389) null mutants are able to establish cell-cell contacts and complete gastrulation but arrest slightly later in development due to failed hypodermal morphogenesis (Costa, et al.). Similarly,
lad-1 null mutants successfully complete gastrulation but exhibit cell-cell position defects later in multiple tissues (L. Chen, personal communication). Since cadherins are important regulators of adhesion during gastrulation in other organisms, we investigated whether other cell-cell adhesion receptors may act redundantly with HMR-1 during early stages of morphogenesis in C. elegans. Interestingly, we find that LAD-1 appears to act cooperatively with HMR-1 during gastrulation. Double RNAi of
hmr-1 and
lad-1 in wild-type embryos results in 100% embryonic lethality due to gastrulation and other morphogenetic defects. We see a similar phenotype when performing
hmr-1(RNAi) on worms that carry a strong loss-of-function mutation in
lad-1/sax-7
(ky146). In embryos, the cadherin-catenin complex localizes to the apical-lateral membrane in areas of cell-cell contact while LAD-1 is distributed in over a wider part of the lateral membrane. This is the first study describing a possible functional relationship between classical cadherins and L1-CAMs in early development. Future studies will focus on elucidating how HMR-1 and LAD-1 act together to modulate cell-cell adhesion during gastrulation.