Notch activity in the nervous system: to switch or not switch?
Notch activity in the nervous system: to switch or not switch?
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DOI：
10.1186/1749-8104-4-36
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发表时间：
2009-10-02
影响因子：
3.6
通讯作者：
Blader P
中科院分区：
文献类型：
--
作者：
Cau E;Blader P
Notch 通路对于发育过程中的细胞命运多样化至关重要。在果蝇中进行的先驱研究以及最近在脊椎动物中进行的研究表明，在神经系统中，当细胞在两种可供选择的命运之间进行选择时，Notch 会被反复使用，这一过程被称为二元命运决定。虽然早期（神经与表皮）命运决定主要涉及Notch对神经命运的抑制作用，但晚期命运决定（神经细胞不同亚型之间的选择）被认为涉及二元开关活动，其中Notch将对一种命运具有指导作用，对另一种命运具有抑制作用。我们根据脊椎动物神经系统的两项最新发现重新检查了这个二元开关模型。首先，在斑马鱼骨骺中，Notch 需要通过抑制一种特定的命运来解决混合身份。其次，在小鼠端脑中，Notch 调节神经祖细胞对 JAK/STAT 通路做出反应的能力，从而诱导星形胶质细胞的命运。在这两种情况下，Notch 都对替代命运没有指导意义，而是与另一个信号通路合作来协调二元命运选择。我们还回顾了在神经亚型多样化的背景下作用于 Notch 下游的分子级联的当前知识，如果要确定 Notch 功能在所涉及的各种细胞环境中作为指导性、许可性或抑制性信号，这是一个至关重要的问题。最后，我们推测这种“非转换”活动如何有助于神经元亚型多样性的扩展。
The Notch pathway is instrumental for cell fate diversification during development. Pioneer studies conducted in Drosophila and more recent work performed in vertebrates have shown that in the nervous system, Notch is reiteratively employed when cells choose between two alternative fates, a process referred to as a binary fate decision. While the early (neural versus epidermal) fate decisions mainly involve an inhibitory effect of Notch on the neural fate, late fate decisions (choice between different subtypes of neural cells) have been proposed to involve a binary switch activity whereby Notch would be instructive for one fate and inhibitory for the other. We re-examine this binary switch model in light of two recent findings made in the vertebrate nervous system. First, in the zebrafish epiphysis, Notch is required to resolve a mixed identity through the inhibition of one specific fate. Second, in the murine telencephalon, Notch regulates the competence of neural progenitors to respond to the JAK/STAT pathway, thereby allowing for the induction of an astrocyte fate. In neither case is Notch instructive for the alternative fate, but rather cooperates with another signalling pathway to coordinate binary fate choices. We also review current knowledge on the molecular cascades acting downstream of Notch in the context of neural subtype diversification, a crucial issue if one is to determine Notch function as an instructive, permissive or inhibitory signal in the various cellular contexts where it is implicated. Finally, we speculate as to how such a 'non-switch' activity could contribute to the expansion of neuronal subtype diversity.
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影响因子：
64.8
作者：
Do, Michael Tri H.;Kang, Shin H.;Xue, Tian;Zhong, Haining;Liao, Hsi-Wen;Bergles, Dwight E.;Yau, King-Wai
通讯作者：
Yau, King-Wai
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作者：
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通讯作者：
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作者：
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通讯作者：
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