Contact-dependent inhibition of cortical neurite growth mediated by notch signaling
Contact-dependent inhibition of cortical neurite growth mediated by notch signaling
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DOI：
10.1126/science.286.5440.741
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发表时间：
1999-10-22
期刊：
影响因子：
56.9
通讯作者：
Rakic, P
中科院分区：
文献类型：
--
作者：
Sestan, N;Artavanis-Tsakonas, S;Rakic, P
发育过程中神经突的旺盛生长随着皮层神经元的成熟而明显减少。对小鼠大脑皮层神经元的体外研究表明，接触介导的Notch信号调节神经元延伸和发育神经突的能力。Notch活性的上调伴随着神经元间接触数量的增加和神经突生长的停止。在具有低Notch活性的神经元中，其容易延伸神经突，Notch活性的上调抑制神经突的延伸或引起神经突的回缩。相反，在建立大量连接后停止生长并显示出高Notch活性的更成熟的神经元中，Notch信号传导的抑制促进了神经突延伸。因此，神经元接触的形成导致Notch受体的激活，导致神经元生长的限制和随后的成熟停滞。
The exuberant growth of neurites during development becomes markedly reduced as cortical neurons mature. In vitro studies of neurons from mouse cerebral cortex revealed that contact-mediated Notch signaling regulates the capacity of neurons to extend and elaborate neurites, Up-regulation of Notch activity was concomitant with an increase in the number of interneuronal contacts and cessation of neurite growth. In neurons with low Notch activity, which readily extend neurites, up-regulation of Notch activity either inhibited extension or caused retraction of neurites. Conversely, in more mature neurons that had ceased their growth after establishing numerous connections and displayed high Notch activity,inhibition of Notch signaling promoted neurite extension. Thus, the formation of neuronal contacts results in activation of Notch receptors, Leading to restriction of neuronal growth and a subsequent arrest in maturity.