Notch activity modulates the responsiveness of neural progenitors to sonic hedgehog signaling.
Notch activity modulates the responsiveness of neural progenitors to sonic hedgehog signaling.
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DOI：
10.1016/j.devcel.2015.03.005
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发表时间：
2015-05-26
影响因子：
11.8
通讯作者：
Novitch, Bennett G.
中科院分区：
文献类型：
--
作者：
Kong, Jennifer H.;Yang, Linlin;Dessaud, Eric;Chuang, Katherine;Moore, Destaye M.;Rohatgi, Rajat;Briscoe, James;Novitch, Bennett G.
在整个神经系统发育过程中，神经干细胞和祖细胞以空间和时间协调的方式产生不同类型的神经元和神经胶质。在腹侧脊髓中，这种多样性大部分是通过Sonic hedgehog（Shh）的形态发生作用出现的。Shh梯度的解释取决于配体的量和暴露的持续时间，但允许延长对Shh的反应的机制还不清楚。我们证明，Notch信号在这个过程中起着至关重要的作用，使神经祖细胞达到足够高水平的Shh通路活性需要指导最腹侧的细胞命运。Notch活性调节Shh受体Patched1的亚细胞定位，门控关键效应物Smoothened向初级纤毛的易位及其下游信号传导活性。这些数据揭示了Notch塑造Shh形态发生梯度的解释并影响细胞命运确定的意想不到的作用。Notch信号的变化改变神经祖细胞的背腹侧身份Notch信号的激活和失活改变细胞对Shh的反应Notch活性是有效运输Smo到初级纤毛所必需的Notch活性调节Shh受体Ptch 1的亚细胞分布腹侧脊髓中的细胞命运分配取决于神经祖细胞解释形态原Shh的能力。Kong和Yang等人显示Notch信号通过调节Shh受体Patched1和下游效应器Smoothened向初级纤毛的运输来调节神经祖细胞对Shh的反应。
Throughout the developing nervous system, neural stem and progenitor cells give rise to diverse classes of neurons and glia in a spatially and temporally coordinated manner. In the ventral spinal cord, much of this diversity emerges through the morphogen actions of Sonic hedgehog (Shh). Interpretation of the Shh gradient depends on both the amount of ligand and duration of exposure, but the mechanisms permitting prolonged responses to Shh are not well understood. We demonstrate that Notch signaling plays an essential role in this process, enabling neural progenitors to attain sufficiently high levels of Shh pathway activity needed to direct the ventral-most cell fates. Notch activity regulates subcellular localization of the Shh receptor Patched1, gating the translocation of the key effector Smoothened to primary cilia and its downstream signaling activities. These data reveal an unexpected role for Notch shaping the interpretation of the Shh morphogen gradient and influencing cell fate determination. Changes in Notch signaling alter the dorsoventral identity of neural progenitors Activation and inactivation of Notch signaling alter cellular responses to Shh Notch activity is required for efficient trafficking of Smo to primary cilia Notch activity regulates the subcellular distribution of the Shh receptor Ptch1 Cell fate assignment in the ventral spinal cord depends on the ability of neural progenitors to interpret the morphogen Shh. Kong and Yang et al. show that Notch signaling tunes neural progenitor responses to Shh by regulating trafficking of the Shh receptor Patched1 and downstream effector Smoothened to primary cilia.
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DOI：
10.1083/jcb.201009069
发表时间：
2011-05-16
期刊：
The Journal of cell biology
影响因子：
--
作者：
Habbig S;Bartram MP;Müller RU;Schwarz R;Andriopoulos N;Chen S;Sägmüller JG;Hoehne M;Burst V;Liebau MC;Reinhardt HC;Benzing T;Schermer B
通讯作者：
Schermer B
影响因子：
9.8
作者：
Dessaud E;Ribes V;Balaskas N;Yang LL;Pierani A;Kicheva A;Novitch BG;Briscoe J;Sasai N
通讯作者：
Sasai N
影响因子：
9.8
作者：
Gaber ZB;Butler SJ;Novitch BG
通讯作者：
Novitch BG
影响因子：
4.2
作者：
Ge, WH;Martinowich, K;Sun, YE
通讯作者：
Sun, YE
影响因子：
4.4
作者：
Han, H;Tanigaki, K;Honjo, T
通讯作者：
Honjo, T