Cell Elongation Induces Laminin a 2 Chain Expression in Mouse Embryonic Mesenchymal Cells: Role in Visceral Myogenesis

Bronchial smooth muscle (SM) mesenchymal cell precursors change their shape from round to spread/elongated while undergoing differentiation. Here we show that this change in cell shape induces the expression of laminin (LM) a 2 chain not present in round mesenchymal cells. LM a 2 expression is reversible and switched on and off by altering the cell’s shape in culture. In comparison, the expression of LM b 1 and g 1 remains unchanged. Functional studies showed that mesenchymal cell spreading and further differentiation into SM are inhibited by an antibody against LM a 2. Dy/dy mice express very low levels of LM a 2 and exhibit congenital muscular dystrophy. Lung SM cells isolated from adult dy/dy mice spread defectively and synthesized less SM a -actin, desmin, and SM-myosin than controls. These deficiencies were completely corrected by exogenous LM-2. On histological examination, dy/dy mouse airways and gastrointestinal tract had shorter SM cells, and lungs from dy/dy mice contained less SM-specific protein. The intestine, however, showed compensatory hyperplasia, perhaps related to its higher contractile activity. This study therefore demonstrated a novel role for the LM a 2 chain in SM myogenesis and showed that its decrease in dy/dy mice results in abnormal SM.