Laminin α5 and integrins α3 and α6 coordinately regulate collective cell migration in vivo

Collective cell migration is essential for development and tissue homeostasis, yet how integrin-extracellular matrix adhesion coordinates migratory force generation in vivo remains poorly understood. Here, we have used the zebrafish posterior lateral line primordium (pLLP) as a model for epithelial collective cell migration. We show that integrins α3 and α6b are expressed in different, yet overlapping, domains of the pLLP and function redundantly to support migration. The systematic combination of itga6b, itga3b and itga3a mutants disrupts integrin β1 localization, increases protrusive activity and impairs migration, revealing a spatially organized, partially redundant adhesion system. We further identify laminin α5 (Lama5) as a key component of the basement membrane (BM) underlying the migrating pLLP. While loss of Lama5 alone compromises BM integrity and pLLP morphology without impairing migration, simultaneous depletion of lama5 and itga6b leads to severe migration defects, with the formation of invadopodia-like structures and ultimately the stalling of migration. Together, these findings reveal a robust, redundant adhesion machinery that ensures persistent collective migration in vivo, and they establish fundamental principles of integrin-mediated adhesion that are relevant to development and disease.