Cell elongation induces laminin α2 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) alpha 2 chain not present in round mesenchymal cells. LM alpha 2 expression is reversible and switched on and off by altering the cell's shape in culture. In comparison, the expression of LM beta 1 and gamma(1) remains unchanged. Functional studies showed that mesenchymal cell spreading and further differentiation into SM are inhibited by an antibody against LM alpha 2. Dy/dy mice express very low levels of LM alpha 2 and exhibit congenital muscular dystrophy. Lung SM cells isolated from adult dy/dy mice spread defectively and synthesized less SM alpha-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 alpha 2 chain in SM myogenesis and showed that its decrease in dy/dy mice results in abnormal SM.