The Thyroid Hormone Receptor α1 Protein Is Expressed in Embryonic Postmitotic Neurons and Persists in Most Adult Neurons

Thyroid hormone is essential for brain development where it acts mainly through the thyroid hormone receptor alpha 1 (TR alpha 1) isoform. However, the potential for the hormone to act in adult neurons has remained undefined due to difficulties in reliably determining the expression pattern of TR proteins in vivo. We therefore created a mouse strain that expresses TR alpha 1 and green fluorescent protein as a chimeric protein from the Thra locus, allowing examination of TR alpha 1 expression during fetal and postnatal development and in the adult. Furthermore, the use of antibodies against other markers enabled identification of TR alpha 1 expression in subtypes of neurons and during specific stages of their maturation. TR alpha 1 expression was first detected in postmitotic cells of the cortical plate in the embryonic telencephalon and preceded the expression of the mature neuronal protein NeuN. In the cerebellum, TR alpha 1 expression was absent in proliferating cells of the external granular layer, but switched on as the cells migrated towards the internal granular layer. In addition, TR alpha 1 was expressed transiently in developing Purkinje cells, but not in mature cells. Glial expression was found in tanycytes in the hypothalamus and in the cerebellum. In the adult brain, TR alpha 1 expression was detected in essentially all neurons. Our data demonstrate that thyroid hormone, unexpectedly, has the capacity to play an important role in virtually all developing and adult neurons. Because the role of TR alpha 1 in most neuronal cell types in vivo is largely unknown, our findings suggest that novel functions for thyroid hormone remain to be identified in the brain. (Molecular Endocrinology 24: 1904-1916, 2010)