Laminin α5 Is Required for Lobar Septation and Visceral Pleural Basement Membrane Formation in the Developing Mouse Lung

Abstract

Laminin α/β/γ heterotrimers are the major noncollagenous components of all basement membranes. To date, five α, three β, and three γ chains have been identified. Laminin α5 is expressed early in lung development and colocalizes with laminin α1. While laminin α1 expression in the lung is restricted to the embryonic period, laminin α5 expression persists throughout embryogenesis and adulthood. Targeted mutation of the mouse laminin α5 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 Lama5−/− 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 α4 in the airway basement membrane. Perturbation of pleural basement membrane formation and right lung septation correlated with absence of laminin α5, which was found to be the only laminin α 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.