Gα subunit coordinates with ephrin-B to balance self-renewal and differentiation in neural progenitor cells.
Gα subunit coordinates with ephrin-B to balance self-renewal and differentiation in neural progenitor cells.
复制标题
Gα亚基与Ephrin-B坐标，以平衡神经祖细胞中的自我更新和分化。
DOI：
10.1002/stem.474
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发表时间：
2010-09
期刊：
影响因子：
5.2
通讯作者：
Lu, Qiang
中科院分区：
文献类型：
--
作者：
Murai, Kiyohito;Qiu, Runxiang;Zhang, Heying;Wang, Jun;Wu, Chen;Neubig, Richard R.;Lu, Qiang
关键词：
哺乳动物大脑的正常发育需要神经前体细胞在精确的时间和空间调节下平衡自我更新和分化，但其潜在机制尚不清楚。在这项研究中，我们确定Gα亚基作为哺乳动物神经发生的正调节因子，与RGS介导的ephrin-B信号通路作为两个相反的力量，以维持发育中的小鼠大脑皮层自我更新和分化之间的平衡。在皮质神经发生过程中，皮质神经前体细胞表达多种Gαi亚基。通过子宫内电穿孔介导的野生型和组成型活性Gαi亚基的表达，Gαi信号传导的激活抵消了皮质神经祖细胞中ephrin-B诱导分化的功能。RGS不敏感的G184 SG αi2基因敲入导致细胞周期提前退出和皮质神经祖细胞减少，并导致晚生皮质神经元产生缺陷，类似于在ephrin-B反向信号通路缺陷的突变小鼠中观察到的情况。本研究揭示了Gα亚基在哺乳动物神经发生中的作用，并揭示了Gα和ephrin-B信号通路协调控制神经前体细胞自我更新和分化之间平衡的发育机制。
Proper development of the mammalian brain requires that neural progenitor cells balance self-renewal and differentiation under precise temporal and spatial regulation, but the underlying mechanisms are not well understood. In this study, we identify Gα subunit as a positive regulator of mammalian neurogenesis, working with the RGS-mediated ephrin-B signaling pathway as two opposing forces to maintain a balance between self-renewal and differentiation in the developing mouse cerebral cortex. Multiple Gαi subunits are expressed by cortical neural progenitor cells during the course of cortical neurogenesis. Activation of Gαi signaling, through in utero electroporation mediated expression of wild-type and constitutively active Gαi subunits, counteracts the function of ephrin-B in cortical neural progenitors to induce differentiation. Genetic knock-in of an RGS-insensitive G184SGαi2 causes early cell cycle exit and a reduction of cortical neural progenitor cells and leads to a defect in the production of late born cortical neurons, similar to what is observed in mutant mice with deficiency in ephrin-B reverse signaling pathway. This study reveals a role of Gα subunit in mammalian neurogenesis and uncovers a developmental mechanism, coordinated by the Gα and ephrin-B signaling pathways, for control of the balance between self-renewal and differentiation in neural progenitor cells.
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影响因子：
2.5
作者：
Noctor, Stephen C.;Martinez-Cerdeno, Veronica;Kriegstein, Arnold R.
通讯作者：
Kriegstein, Arnold R.
影响因子：
7.8
作者：
Cho, Hyeseon;Kehrl, John H.
通讯作者：
Kehrl, John H.
DOI：
10.1073/pnas.0308600100
发表时间：
2004-03-02
影响因子：
11.1
作者：
Haubensak, W;Attardo, A;Huttner, WB
通讯作者：
Huttner, WB
影响因子：
13.9
作者：
Kriegstein A;Alvarez-Buylla A
通讯作者：
Alvarez-Buylla A
影响因子：
64.5
作者：
Lu, Q;Sun, EE;Flanagan, JG
通讯作者：
Flanagan, JG