Novel genes upregulated when NOTCH signalling is disrupted during hypothalamic development.

Novel genes upregulated when NOTCH signalling is disrupted during hypothalamic development.
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DOI:
10.1186/1749-8104-8-25
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发表时间:
2013-12-23
期刊:
影响因子:
3.6
通讯作者:
Dupé V
Dupé V
中科院分区:
生物学3区
文献类型:
--
作者:
Ratié L;Ware M;Barloy-Hubler F;Romé H;Gicquel I;Dubourg C;David V;Dupé V

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在发育过程中,多能祖细胞产生不同的神经元类型和亚型对于在成人中枢神经系统中组装功能性神经回路至关重要。众所周知,通过抑制原神经基因的Notch信号通路是脊椎动物中枢神经系统神经发生的关键调节因子。然而,Notch 在下丘脑形成过程中的作用及其下游效应器仍不清楚。在这里,我们暂时阻断了鸡胚胎中的 Notch 活性,并使用全局基因表达分析来提供证据,证明 Notch 信号传导通过侧抑制调节早期发育的下丘脑中神经元的生成。最重要的是,我们利用该模型来识别 Notch 信号传导的新靶点,例如 Tagln3 和 Chga,它们在下丘脑神经元核中表达。这些数据为下丘脑神经元的早期生成提供了重要进展。我们证明,在下丘脑早期发育过程中抑制 Notch 信号传导可以增强几种新标记物的表达。这些基因必须被视为Notch/原神经网络的重要新靶标。
The generation of diverse neuronal types and subtypes from multipotent progenitors during development is crucial for assembling functional neural circuits in the adult central nervous system. It is well known that the Notch signalling pathway through the inhibition of proneural genes is a key regulator of neurogenesis in the vertebrate central nervous system. However, the role of Notch during hypothalamus formation along with its downstream effectors remains poorly defined. Here, we have transiently blocked Notch activity in chick embryos and used global gene expression analysis to provide evidence that Notch signalling modulates the generation of neurons in the early developing hypothalamus by lateral inhibition. Most importantly, we have taken advantage of this model to identify novel targets of Notch signalling, such as Tagln3 and Chga, which were expressed in hypothalamic neuronal nuclei. These data give essential advances into the early generation of neurons in the hypothalamus. We demonstrate that inhibition of Notch signalling during early development of the hypothalamus enhances expression of several new markers. These genes must be considered as important new targets of the Notch/proneural network.
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