THYROXINE-DEPENDENT REGULATION OF INTEGRIN-LAMININ INTERACTIONS IN ASTROCYTES

Adhesive interactions among the extracellular matrix protein laminin, cell surface receptors known as integrins, and the microfilament netwo rk play a fundamental role in the regulation of neural cell migration during brain development. The disturbed neuronal migration that occurs when thyroid hormone is lacking during early neonatal life contribute s to the profound morphological alterations characteristic of the cret inous brain. We have previously shown that thyroid hormone determines the organization of the microfilament network in astrocytes by regulat ing the polymerization of F-actin fibers. In this paper, we examined w hether T-4-dependent alterations in microfilament organization affecte d astrocyte-laminin interactions. We show that T-4-treated astrocytes readily attached to laminin, whereas attachment of thyroid hormone-def icient cells to laminin was delayed. T-4-dependent cell attachment to laminin was completely abolished by blocking integrin recognition site s with site-specific peptides or by depolymerizing the microfilaments with dihydrocytochalasin B. We also show that T-4 was required for int egrin clustering and focal contact formation in astrocytes attached to laminin. Thus, T-4 dynamically regulates interactions between integri ns and laminin via modulation of microfilament organization in astrocy tes. The T-4-dependent regulation of laminin-integrin interactions pro vides a mechanism by which this morphogenic hormone can influence neur onal migration and development.