Journal
MOLECULAR AND CELLULAR NEUROSCIENCE
Volume 44, Issue 1, Pages 68-77Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mcn.2010.02.004
Keywords
Cerebellum; Thyroid hormone; TR beta; Nuclear receptors; Foliation; Bergmann glia
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Funding
- Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
- Sociedade Brasileira de Endocrinologia e Metabologia (SBEM)
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Cerebellar development on the postnatal period is mainly characterized by cellular proliferation in the external granular layer (EGL) followed by migration of granular cells in the molecular layer through the Bergmann glia (BG) fibers in order to form the granular layer in the adult. All these events are drastically affected by thyroid hormones (TH), which actions are mainly mediated by alpha (TR alpha) and beta (TR beta) nuclear receptor isoforms. Here, we analyzed the effects of a natural human mutation (337T) in the TR beta locus, which impairs T3 binding to its receptor, on the mouse cerebellum ontogenesis. We report that target inactivation of TR beta-TH binding leads to a smaller cerebellum area characterized by impaired lamination and foliation. Further. TR beta mutant mice presented severe deficits in proliferation of granular precursors, arborization of Purkinje cells and organization of BG fibers. Together, our data suggest that the action of TH via TR beta regulates important events of cerebellar ontogenesis contributing to a better understanding of some neuroendocrine disorders. Further, our data correlate TR beta with cerebellar foliation, and provide, for the first time, evidence of a receptor-mediated mechanism underlying TH actions on this event. (C) 2010 Elsevier Inc. All rights reserved.
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