A Bimodal Influence of Thyroid Hormone on Cerebellum Oligodendrocyte Differentiation

Thyroid hormone (T-3) can trigger a massive differentiation of cultured oligodendrocytes precursor cells (OPC) by binding the nuclear T-3 receptor alpha 1 (TR alpha 1). Whether this reflects a physiological function of TR alpha 1 remains uncertain. Using a recently generated mouse model, in which CRE/loxP recombination is used to block its function, we show that TR alpha 1 acts at two levels for the in vivo differentiation of OPC in mouse cerebellum. At the early postnatal stage, it promotes the secretion of several neurotrophic factors by acting in Purkinje neurons and astrocytes, defining an environment suitable for OPC differentiation. At later stages, TR alpha 1 acts in a cell-autonomous manner to ensure the complete arrest of OPC proliferation. These data explain contradictory observations made on various models and outline the importance of T-3 signaling both for synchronizing postnatal neurodevelopment and restraining OPC proliferation in adult brain. (Molecular Endocrinology 26: 608-618, 2012)