Thyroid hormone action during brain development: More questions than answers

Thyroid hormone is essential for proper brain development since it acts on processes such as neuronal migration and differentiation, myelination and synaptogenesis. In this review, we summarize the consequences of thyroid hormone deficiency for brain development with special focus on the cerebellum, an important target of thyroid action. In addition, we discuss the role of iodothyronine deiodinases and thyroid hormone transporters in regulating local thyroid hormone concentrations as well as current knowledge about the function of thyroid hormone receptors and their target genes during brain maturation. Despite considerable progress in recent years in deciphering thyroid hormone signaling pathways we still know very little on the molecular level by which mode of action thyroid hormone exerts its cell-specific effects. Hence, we will particularly address the open questions that remain to be addressed in order to better understand the role of thyroid hormone in brain development.