Fibronectin and fibronectin receptors in lung development.

Fibronectin (FN) is a cell adhesive extracellular matrix protein highly expressed in developing lungs. Although the role of FN in lung development remains to be elucidated, several observations suggest that it plays important roles in many developmental processes. In vitro, FN can affect the migration, proliferation, differentiation, and even apoptosis of various cell types, all considered necessary for organogenesis. The cellular effects of FN are primarily mediated by cell surface heterodimeric receptors of the integrin family. Ligand binding to these receptors triggers the activation of intracellular signaling events responsible for alterations in gene transcription and, ultimately, cell function. Immunohistochemical analysis of embryos revealed increased deposition of FN during the pseudoglandular stage of lung development, coinciding with the period of branching morphogenesis. This observation, together with the strategic location of FN around developing airways predominantly at cleft sites, suggests a role in airways formation. This hypothesis is supported by studies showing that reagents capable of preventing FN-FN receptor binding inhibit branching morphogenesis in murine lung explants. Less is known about the potential role of FN in other aspects of lung development. However, in vitro studies suggest that FN may affect vessel formation, alveolar epithelial cell differentiation and lung growth and maturation.