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 network 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 contributes to the profound morphological alterations characteristic of the cretinous brain. We have previously shown that thyroid hormone determines the organization of the microfilament network in astrocytes by regulating the polymerization of F-actin fibers. In this paper, we examined whether T4-dependent alterations in microfilament organization affected astrocyte-laminin interactions. We show that T4-treated astrocytes readily attached to laminin, whereas attachment of thyroid hormone-deficient cells to laminin was delayed. T4-dependent cell attachment to laminin was completely abolished by blocking integrin recognition sites with site-specific peptides or by depolymerizing the microfilaments with dihydrocytochalasin B. We also show that T4 was required for integrin clustering and focal contact formation in astrocytes attached to laminin. Thus, T4 dynamically regulates interactions between integrins and laminin via modulation of microfilament organization in astrocytes. The T4-dependent regulation of laminin-integrin interactions provides a mechanism by which this morphogenic hormone can influence neuronal migration and development.