LAD-1, the Caenorhabditis elegans L1CAM homologue, participates in embryonic and gonadal morphogenesis and is a substrate for fibroblast growth factor receptor pathway-dependent phosphotyrosine-based signaling

This study shows that L1-like adhesion (LAD-1), the sole Caenorhabditis ele gans homologue of the L1 family of neuronal adhesion molecules, is required for proper development of the germline and the early embryo and embryonic and gonadal morphogenesis. In addition, the ubiquitously expressed LAD-1, w hich binds to ankyrin-G, colocalizes with the C. elegans ankyrin, UNC-44, i n multiple tissues at sites of cell-cell contact. Finally, we show that LAD -1 is phosphorylated in a fibroblast growth factor receptor (FGFR) pathway- dependent manner on a tyrosine residue in the highly conserved ankyrin-bind ing motif, FIGQY, which was shown previously to abolish the L1 family of ce ll adhesion molecule (L1 CAM) binding to ankyrin in cultured cells. Immunof luorescence studies revealed that FIGQY-tyrosine-phosphorylated LAD-1 does not colocalize with nonphosphorylated LAD-1 or UNC-44 ankyrin but instead i s localized to sites that undergo mechanical stress in polarized epithelia and axon-body wall muscle junctions. These findings suggest a novel ankyrin -independent role for LAD-1 related to FGFR signaling. Taken together, thes e results indicate that L1CAMs constitute a family of ubiquitous adhesion m olecules, which participate in tissue morphogenesis and maintaining tissue integrity in metazoans.