Normal timing of oligodendrocyte development depends on thyroid hormone receptor alpha 1 (TRα1)
Normal timing of oligodendrocyte development depends on thyroid hormone receptor alpha 1 (TRα1)
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DOI：
10.1093/emboj/cdf662
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发表时间：
2002-12-02
期刊：
影响因子：
11.4
通讯作者：
Raff, M
中科院分区：
文献类型：
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作者：
Billon, N;Jolicoeur, C;Raff, M
少突胶质细胞的发育时间在体外和体内都受到甲状腺激素(TH)的调节，但目前还不确定哪种TH受体介导了这一调节。TH通过由两个基因TRAlpha和TRbeta编码的核受体发挥作用。在这里，我们通过显示TRalpha1-/-小鼠出生后第7天(P7)和P14视神经中的少突胶质细胞数量比正常减少，为TRalpha1受体亚型在体内的参与提供了直接证据。我们证明了TRalpha1介导了TH对少突胶质前体细胞的正常分化促进作用：与野生型OPC不同，出生后的TRalpha1-/-OPC不能在培养中对TH做出反应而停止分裂和分化。我们还发现，TRalpha1的过表达加速了培养中的少突胶质细胞的分化，这表明TRalpha1的表达水平通常对TH依赖的OPC的分化是有限的。最后，我们提供的证据表明，TRpha的抑制亚型不太可能在OPC分化的时间上发挥作用。
The timing of oligodendrocyte development is regulated by thyroid hormone (TH) in vitro and in vivo, but it is still uncertain which TH receptors mediate this regulation. TH acts through nuclear receptors that are encoded by two genes, TRalpha and TRbeta. Here, we provide direct evidence for the involvement of the TRalpha1 receptor isoform in vivo, by showing that the number of oligodendrocytes in the postnatal day 7 (P7) and P14 optic nerve of TRalpha1-/- mice is decreased compared with normal. We demonstrate that TRalpha1 mediates the normal differentiation-promoting effect of TH on oligodendrocyte precursor cells (OPCs): unlike wild-type OPCs, postnatal TRalpha1-/- OPCs fail to stop dividing and differentiate in response to TH in culture. We also show that overexpression of TRalpha1 accelerates oligodendrocyte differentiation in culture, suggesting that the level of TRalpha1 expression is normally limiting for TH-dependent OPC differentiation. Finally, we provide evidence that the inhibitory isoforms of TRalpha are unlikely to play a part in the timing of OPC differentiation.