Zonula adherens formation in Caenorhabditis elegans requires dlg-1, the homologue of the Drosophila gene discs large

The correct assembly of junction components, such as E-cadherin and beta -c atenin, into the zonula adherens is fundamental for the function of epithel ia, both in flies and in vertebrates. In C. elegans, however, the cadherin- catenin system is not essential for general adhesion, raising the question as to the genetic basis controlling junction morphogenesis in nematodes. He re we show that dlg-1, the C. elegans homologue of the Drosophila tumour-su ppressor gene discs-large, plays a crucial role in epithelial development. DLG-1 is restricted to adherens junctions of all embryonic epithelia, which contrasts with the localisation of the Drosophila and vertebrate homologue s in septate and tight junctions, respectively. Proper localisation of DLG- 1 requires the basolateral LET-413 protein, but is independent of the cadhe rin-catenin system. Embryos in which dlg-1 activity was eliminated by RNA-m ediated interference fail to form a continuous belt of junction-associated antigens and arrest development. Loss of dlg-1 activity differentially affe cts localisation of proteins normally enriched apically to the zonula adher ens. While the distribution of an atypical protein kinase C (PKC-3) and oth er cytoplasmic proteins (PAR-3, PAR-6) is not affected in dlg-1 (RNAi) embr yos, the transmembrane protein encoded by crb-1, the C. elegans homologue o f Drosophila crumbs, is no longer concentrated in this domain. In contrast to Drosophila, however, crb-1 and a second crb-like gene are not essential for epithelial development in C. elegans. Together the data indicate that s everal aspects of the spatial organisation of epithelial cells and its gene tic control differ between flies, worms, and vertebrates, while others are conserved. The molecular nature of DLG-1 makes it a likely candidate to par ticipate in the organisation of a protein scaffold that controls the assemb ly of junction components into the zonula adherens. (C) 2001 Academic Press .