Laminin isoforms and lung development: All isoforms are not equal

Laminins are a major component of basement membranes. Each laminin molecule is a heterotrimeric glycoprotein composed of one α, one β, and one γ chain. Fifteen laminin isoforms exist, assembled from various combinations of 5α, 3β, and 3γ chains. The embryonic lung has abundant laminin isoforms. Increasing evidence suggests that different laminin isoforms have unique functions in lung development. Studies of embryonic lung explants and organotypic co-cultures show that laminin α1 and laminin 111 are important for epithelial branching morphogenesis and that laminin α2 and laminin 211 have a role in smooth muscle cell differentiation. In vivo studies of laminin α5-deficient mice indicate that this laminin chain, found in laminins 511 and 521, is essential for normal lobar septation in early lung development and normal alveolization and distal epithelial cell differentiation and maturation in late lung development. However, not all of the laminin chains present in the developing lung appear to be necessary for normal lung development since laminin α4 null mice do not have obvious lung abnormalities and laminin γ2 null mice have only minimal changes in lung development. The mechanisms responsible for the lung phenotypes in mice with laminin mutations are unknown, but it is clear that multiple laminin isoforms are crucial for lung development and that different laminin isoforms exhibit specific, non-overlapping functions.