| Angeles Rodriguez-Pena's CV |
Myelination and oligodendrocyte population dynamics studied in thyroid hormone receptor knockout mice: specific effects of thyroid hormone receptor beta
( Porlan, E. )
Lack of thyroid hormone (T3) in humans leads to cretinism. Cretinism is also found in other mammals but the underlying mechanism of this condition is not well understood. Hypothyroidism produces severe delays and reductions in the myelination of the central nervous system. However, the extent of this effect is different in the various brain regions. It is unclear what causes this problem but it is presumed to reflect abnormal development of oligodendrocytes. Our hypothesis is that a decrease in the number of differentiated oligodendrocytes (OL) explains the marked reduction in the levels of myelin proteins. Accordingly, T3 promotes oligodendrocyte differentiation in vitro. T3 regulates gene expression through its interaction with nuclear receptors (encoded by two genes TR alpha and beta) that act as ligand dependent transcription factors. Interestingly, ectopic expression of TRbeta in fibroblasts inhibits cell proliferation, and its expression is confined to the pre- and differentiated OL. Our aim is to study in vivo (by the use of transgenic mice devoid of each T3 receptor isoform) the specific contribution of the T3 receptor isoforms to oligodendrocyte development and linage determination in spinal cord and telencephalon. We will also establish the molecular basis for the antiproliferative action of TRbeta and how this effect contributes to the oligodendrocyte differentiation process.