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 alpha, one beta, and one gamma chain. Fifteen laminin isoforms exist, assembled from various combinations of 5 alpha, 3 beta, and 3 gamma 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 alpha 1 and laminin 111 are important for epithelial branching morphogenesis and that laminin alpha 2 and laminin 211 have a role in smooth muscle cell differentiation. In vivo studies of laminin alpha 5-deficient mice indicate that this laminin chain, found in laminins 511 and 52 1, 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 alpha 4 null mice do not have obvious lung abnormalities and laminin gamma 2 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. (c) 2006 Elsevier Inc. All rights reserved.