Laminin [alpha]5 is required for lobar septation and visceral pleural basement membrane formation in the developing mouse lung

Laminin [alpha/beta/gamma] heterotrimers are the major noncollagenous components of all basement membranes. To date, five [alpha], three [beta], and three [gamma] chains have been identified. Laminin [alpha]5 is expressed early in lung development and colocalizes with laminin [alpha]l. While laminin [alpha]1 expression in the lung is restricted to the embryonic period, laminin [alpha]5 expression persists throughout embryogenesis and adulthood. Targeted mutation of the mouse laminin [alpha]5 gene Lama5 causes embryonic lethality at E14-E17 associated with exencephaly, syndactyly, placentopathy, and kidney defects, all attributable to abnormal basement membranes. In this investigation, lung development in Lama[5.sup.-/-] mice up to E16.5 was examined. We observed normal lung branching morphogenesis and vasculogenesis, but incomplete lobar septation and absence of the visceral pleura basement membrane. Preservation of branching morphogenesis was associated with ectopic deposition of laminin [alpha]4 in the airway basement membrane. Perturbation of pleural basement membrane formation and right lung septation correlated with absence of laminin [alpha]5, which was found to be the only laminin [alpha] chain present in the normal visceral pleura basement membrane. Our finding of normal lung branching morphogenesis with abnormal lobar septation demonstrates that these processes are not obligatorily linked. Key Words: laminin; lung development; basement membrane; visceral pleura; lobar septation.