beta(1)-integrins are involved in migration of human fetal tracheal epithelial cells and tubular morphogenesis

Development of human fetal airways requires interaction of the respiratory epithelium and the extracellular matrix through integrins. Nevertheless, th e specific roles of beta(1)-integrins during development and tubular morpho genesis are still unknown. To analyze beta(1)-integrin localization and inf luence during migration, we developed a model of human fetal tracheal expla nts growing on collagen and overlaid with a second layer of collagen to for m a sandwich. In this configuration, cord and tubule formation proceeded no rmally but were inhibited by incubation with anti-beta(1)-integrin subunit antibodies. On a collagen matrix, beta(1)-integrins were immunolocalized on the entire plasma membrane of migrating epithelial cells and almost exclus ively on the basal plasma membrane of nonmigratory epithelial cells. In a s andwich configuration, beta(1)-integrins became detectable in the cytoplasm of epithelial cells. Coating cultures with collagen transiently altered th e morphology of migrating cells and their speed and direction of migration, whereas incubation with anti-beta(1)-integrin subunit antibodies irreversi bly altered these parameters. These observations suggest that the matrix en vironment, by modulating beta(1)-integrin expression patterns, plays a key role during tubular morphogenesis of human fetal tracheal epithelium, princ ipally by modulating epithelial cell migration.