Thyroid hormone regulates the expression of the sonic hedgehog signaling pathway in the embryonic and adult Mammalian brain.
Thyroid hormone regulates the expression of the sonic hedgehog signaling pathway in the embryonic and adult Mammalian brain.
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DOI：
10.1210/en.2010-1396
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发表时间：
2011-05
期刊：
影响因子：
4.8
通讯作者：
Vaidya VA
中科院分区：
文献类型：
--
作者：
Desouza LA;Sathanoori M;Kapoor R;Rajadhyaksha N;Gonzalez LE;Kottmann AH;Tole S;Vaidya VA
在母体或成年甲状腺激素扰动后，形态发生素Shh及其受体的表达在胚胎和成年哺乳动物大脑中受到强有力的调节。甲状腺激素对于未成熟和成年哺乳动物大脑的发育和可塑性很重要。一些甲状腺激素反应基因在特定的发育时间窗口内受到调节，在整个生命周期中受到的影响相对较小。我们提供了新的证据，证明甲状腺激素在早期胚胎和成人前脑中调节关键发育成形素音刺猬 (Shh) 及其辅助受体修补 (Ptc) 和平滑 (Smo) 的表达。母亲甲状腺功能减退症和甲状腺功能亢进症在胎儿甲状腺激素合成之前的阶段双向影响胚胎前脑信号中心的 Shh mRNA。此外，甲状腺功能减退母鼠胚胎前脑中的 Smo 和 Ptc 表达显着降低。成人发病的甲状腺激素扰动也双向调节Shh通路的表达，甲状腺功能亢进后Shh、Ptc和Smo显着诱导，而甲状腺功能减退脑中Smo表达下降。短期 T3 给药导致皮质 Shh mRNA 表达的显着诱导，并且还增强了 Shh+/LacZ 小鼠中报告基因的表达。此外，皮质神经元培养物的急性 T3 处理导致 Shh mRNA 快速显着增加，表明有直接作用。对成人新皮质进行的染色质免疫沉淀测定表明，急性 T3 给药后，Shh 启动子处的组蛋白乙酰化增强，进一步支持 Shh 是甲状腺激素反应基因。我们的研究结果表明，母体和成年时甲状腺功能正常状态的扰动会导致胚胎和成年前脑中Shh通路的强烈和区域特异性变化，这表明Shh可能是甲状腺激素特定神经发育作用的机制联系。
Expression of the morphogen Shh and its receptors is robustly regulated in the embryonic and adult mammalian brain following maternal or adult-onset thyroid hormone perturbations. Thyroid hormone is important for development and plasticity in the immature and adult mammalian brain. Several thyroid hormone-responsive genes are regulated during specific developmental time windows, with relatively few influenced across the lifespan. We provide novel evidence that thyroid hormone regulates expression of the key developmental morphogen sonic hedgehog (Shh), and its coreceptors patched (Ptc) and smoothened (Smo), in the early embryonic and adult forebrain. Maternal hypo- and hyperthyroidism bidirectionally influenced Shh mRNA in embryonic forebrain signaling centers at stages before fetal thyroid hormone synthesis. Further, Smo and Ptc expression were significantly decreased in the forebrain of embryos derived from hypothyroid dams. Adult-onset thyroid hormone perturbations also regulated expression of the Shh pathway bidirectionally, with a significant induction of Shh, Ptc, and Smo after hyperthyroidism and a decline in Smo expression in the hypothyroid brain. Short-term T3 administration resulted in a significant induction of cortical Shh mRNA expression and also enhanced reporter gene expression in Shh+/LacZ mice. Further, acute T3 treatment of cortical neuronal cultures resulted in a rapid and significant increase in Shh mRNA, suggesting direct effects. Chromatin immunoprecipitation assays performed on adult neocortex indicated enhanced histone acetylation at the Shh promoter after acute T3 administration, providing further support that Shh is a thyroid hormone-responsive gene. Our results indicate that maternal and adult-onset perturbations of euthyroid status cause robust and region-specific changes in the Shh pathway in the embryonic and adult forebrain, implicating Shh as a possible mechanistic link for specific neurodevelopmental effects of thyroid hormone.
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DOI：
10.1111/j.1460-9568.2005.04317.x
发表时间：
2005-10
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Banerjee SB;Rajendran R;Dias BG;Ladiwala U;Tole S;Vaidya VA
通讯作者：
Vaidya VA
影响因子：
2.5
作者：
Bragina, Olga;Sergejeva, Svetlana;Zarkovsky, Aleksandr
通讯作者：
Zarkovsky, Aleksandr
影响因子：
5.3
作者：
Amankulor, Nduka M.;Hambardzumyan, Dolores;Holland, Eric C.
通讯作者：
Holland, Eric C.
影响因子：
4.8
作者：
Ausó, E;Lavado-Autric, R;Berbel, P
通讯作者：
Berbel, P
影响因子：
3.5
作者：
Desouza, LA;Ladiwala, U;Vaidya, VA
通讯作者：
Vaidya, VA