Integrin α8β1 Is Critically Important for Epithelial–Mesenchymal Interactions during Kidney Morphogenesis

AbstractWe present genetic evidence that integrins regulate epithelial–mesenchymal interactions during organogenesis. Mice with a mutation in the α8 gene do not express the integrin α8β1 and exhibit profound deficits in kidney morphogenesis. In wild-type animals, inductive interactions between the ureteric epithelium and metanephric mesenchyme are essential for kidney morphogenesis. In α8 mutant homozygotes, growth and branching of the ureteric bud and recruitment of mesenchymal cells into epithelial structures are defective. Consistent with these phenotypes, α8 expression is induced in mesenchymal cells upon contact with the ureter. Since none of its previously identified ligands appears likely to mediate the essential functions of α8β1 in kidney morphogenesis, we have used an α8β1–alkaline phosphatase chimera to localize novel ligand(s) in the growing ureter. The distribution of these ligand(s) makes them strong candidates for regulators of kidney morphogenesis