The goal of this proposal is the characterization of mechanisms by which thyroid hormone can influence neuronal migration in the developing brain by regulating the ability of brain cells to interact with their extracellular environment. The first part of the proposal will characterize the effects of thyroid hormone on synthesis and distribution of laminin and fibronectin by astrocytes by in vivo and in vitro approaches. The second part will examine the effects of altered integrin ECM interaction on neurite outgrowth. The final section will examine how thyroid hormone can regulate ECM derived clues by altering integrin mediated activation of intracellular signaling pathways. These studies will provide a possible mechanism for the profound effects of thyroid hormone on the developing brain. In addition, the studies will begin to address some of the fundamental questions of how cells interact, respond and adapt to their environment.
