Integrin β1 activity is required for cardiovascular formation in zebrafish.

Integrins are transmembrane molecules that facilitate cell-to-cell and cell-to-extracellular matrix (ECM) interactions. Integrin molecules are heterodimers that consist of α- and β-subunits. The integrin β1 gene is widely expressed in vivo and is the major β molecule in many tissues; however, tissue-specific roles of integrin β1 are still elusive. In this study, we investigated integrin β1 function in endothelial cells of zebrafish. An integrin β1b mutant zebrafish exhibited morphological abnormalities in blood vessel formation, cephalic hemorrhage and a decreased responsiveness to tactile stimulation during development. To determine the role of integrin β1b in vascular formation, we developed a Gal4/UAS-mediated conditional inactivation of integrin β1 by expressing the cytoplasmic region of integrin β1 that acts as a dominant-negative (DN) isoform. Expression of integrin β1 DN in endothelial cells induced blood vessel abnormalities as in integrin β1b mutants. These results show that endothelial cells require integrin activity for the formation and/or maintenance of blood vessels in zebrafish. Furthermore, our time-lapse recording visualized the breakpoint of cephalic vessels and the hemorrhage onset. Taken together, our tissue-specific inactivation of integrin β1 in zebrafish is powerful tools for functional analysis of integrin β1 in developing tissues.