Thyroid hormones and neurovascular development: An integrated framework.

Thyroid hormones (THs) are essential regulators of brain development known for their roles in neuronal proliferation, migration, differentiation, and maturation. However, brain development relies on coordinated interactions among neural, glial, vascular, and extracellular matrix components, supporting a broader role for TH beyond neuronal effects. Here, we examine how spatial regulation of TH availability contributes to neurovascular development by integrating findings from developmental animal models, human fetal tissue, cerebral organoids, and TH transport disorders. We discuss the molecular mechanisms controlling TH availability and examine how TH signaling influences angiogenesis, astrocyte maturation, extracellular matrix remodeling, and blood-brain barrier formation. Together, these findings support a conceptual framework in which local regulation of TH action may coordinate signaling among vascular, glial, and neural compartments during neurovascular unit assembly. This perspective provides a hypothesis-generating framework for understanding how impaired TH signaling may affect multiple developmental processes simultaneously, including maternal thyroid dysfunction and transport disorders.