Roles for βpat-3 Integrins in Development and Function of Caenorhabditis elegans Muscles and Gonads

Heterodimeric integrin receptors for extracellular matrix (ECM) play vital roles in bidirectional signaling during tissue development, organization, remodeling, and repair. The β integrin subunit cytoplasmic domain is essential for transmission of many of these signals and overexpression of an unpaired β tail in cultured cells inhibits endogenous integrins. Unlike vertebrates, which have at least nine β subunit genes, the nematode Caenorhabditis elegans expresses only one β subunit (βpat-3), and a null mutation in this gene causes embryonic lethality. To determine the functions of integrins during larval development and in adult tissues, we have taken a dominant negative approach by expression of an HA-βtail transgene composed of a hemagglutinin (HA) epitope tag extracellular domain connected to the βpat-3 transmembrane and cytoplasmic domains. Expression of this transgene in muscle and gonad, major sites of integrin expression, caused a variety of pheno-types dependent on the level of transgene expression. Abnormalities in body wall and sex muscles led to uncoordinated movement and egg-laying defects. Significant anomalies in migration and pathfinding were caused by tissue-specific expression of HA-βtail in the distal tip cells (DTC), the cells that direct gonad morphogenesis. A pat-3 gene with Tyr to Phe mutations in the cytoplasmic domain was able to rescue pat-3 null animals but also showed DTC migration defects. These results show that βpat-3 plays important roles in post-embryonic organogenesis and tissue function.