Integrin αV is necessary for gastrulation movements that regulate vertebrate body asymmetry

Integrin alpha V can form heterodimers with several beta subunits to mediate cell-cell and cell-extracellular matrix interactions. During zebrafish gastrulation, alpha V is expressed maternally and zygotically. Here, we used a morpholino-mediated alpha V knockdown strategy to study alpha V function. Although alpha V morphants displayed vascular defects, they also exhibited left-right body asymmetry defects affecting multiple visceral organs. This was preceded by mislocalization of dorsal forerunner cells (DFCs) and malformation of the Kupffer's vesicle (KV) laterality organ. These defects were rescued with morpholino-resistant alpha V mRNA. Like alpha V, integrin beta 1b was expressed in DFCs, and beta 1b knockdown largely recapitulated the laterality phenotype of alpha V morphants. When tracked in realtime, individual DFCs of both morphants showed defects in DFC migration, preventing them from organizing into a KV of normal shape and size. Thus, we propose that alpha V beta 1b mediates cellular interactions that are necessary for DFC clustering and movements necessary for Kupffer's vesicle formation, uncovering an early contribution of integrins to the regulation of vertebrate laterality.