This study shows that L1-like adhesion (LAD-1), the sole Caenorhabditis elegans 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, which binds to ankyrin-G, colocalizes with the C. elegans ankyrin, UNC-44, in 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-binding motif, FIGQY, which was shown previously to abolish the L1 family of cell adhesion molecule (L1CAM) binding to ankyrin in cultured cells. Immunofluorescence studies revealed that FIGQY-tyrosine–phosphorylated LAD-1 does not colocalize with nonphosphorylated LAD-1 or UNC-44 ankyrin but instead is 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, these results indicate that L1CAMs constitute a family of ubiquitous adhesion molecules, which participate in tissue morphogenesis and maintaining tissue integrity in metazoans.

The Caenorhabditis elegans genome encodes one α spectrin subunit, a β spectrin subunit (β-G), and a β-H spectrin subunit. Our experiments show that the phenotype resulting from the loss of the C. elegans α spectrin is reproduced by tandem depletion of both β-G and β-H spectrins. We propose that α spectrin combines with the β-G and β-H subunits to form α/β-G and α/β-H heteromers that perform the entire repertoire of spectrin function in the nematode. The expression patterns of nematode β-G spectrin and vertebrate β spectrins exhibit three striking parallels including: (1) β spectrins are associated with the sites of cell–cell contact in epithelial tissues; (2) the highest levels of β-G spectrin occur in the nervous system; and (3) β spec-trin-G in striated muscle is associated with points of attachment of the myofilament apparatus to adjacent cells. Nematode β-G spectrin associates with plasma membranes at sites of cell–cell contact, beginning at the two-cell stage, and with a dramatic increase in intensity after gastrulation when most cell proliferation has been completed. Strikingly, depletion of nematode β-G spectrin by RNA-mediated interference to undetectable levels does not affect the establishment of structural and functional polarity in epidermis and intestine. Contrary to recent speculation, β-G spectrin is not associated with internal membranes and depletion of β-G spectrin was not associated with any detectable defects in secretion. Instead β-G spectrin-deficient nematodes arrest as early larvae with progressive defects in the musculature and nervous system. Therefore, C. elegans β-G spectrin is required for normal muscle and neuron function, but is dispensable for embryonic elongation and establishment of early epithelial polarity. We hypothesize that heteromeric spectrin evolved in metazoans in response to the needs of cells in the context of mechanically integrated tissues that can withstand the rigors imposed by an active organism.