The phosphatase PP4c controls spindle orientation to maintain proliferative symmetric divisions in the developing neocortex.
The phosphatase PP4c controls spindle orientation to maintain proliferative symmetric divisions in the developing neocortex.
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DOI：
10.1016/j.neuron.2013.05.027
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发表时间：
2013-07-24
期刊：
影响因子：
16.2
通讯作者：
Knoblich JA
中科院分区：
文献类型：
--
作者：
Xie Y;Jüschke C;Esk C;Hirotsune S;Knoblich JA
在发育中的新皮层中，祖细胞在通过多轮不对称细胞分裂产生皮层神经元之前通过对称分裂进行扩增。在这里，我们表明，有丝分裂纺锤体的方向起着至关重要的作用，在调节这两种分裂模式之间的过渡。我们证明，蛋白磷酸酶PP4c调节纺锤体的方向在早期皮质祖细胞。去除PP4c后，有丝分裂纺锤体不能平行于神经上皮表面定向，祖细胞以随机方向分裂。结果，它们的分裂变得不对称，神经发生过早开始。生物化学和遗传学实验表明，PP4c通过使微管结合蛋白Ndel1去磷酸化，从而使复合物与Lis1形成功能性纺锤体取向复合物。我们的研究结果确定了皮质发育的关键调节因子，并表明祖细胞分裂方向的变化是对称和不对称细胞分裂之间过渡的原因。PP4c是皮质祖细胞纺锤体定向所必需的。PP4c的缺失导致神经元过早分化。在皮质发育过程中，纺锤体方向的重要性。他们表明，在神经发生开始时的一个独特的时间窗口期间，需要水平纺锤体取向，以确保对称分裂和维持祖细胞库。
In the developing neocortex, progenitor cells expand through symmetric division before they generate cortical neurons through multiple rounds of asymmetric cell division. Here, we show that the orientation of the mitotic spindle plays a crucial role in regulating the transition between those two division modes. We demonstrate that the protein phosphatase PP4c regulates spindle orientation in early cortical progenitor cells. Upon removing PP4c, mitotic spindles fail to orient in parallel to the neuroepithelial surface and progenitors divide with random orientation. As a result, their divisions become asymmetric and neurogenesis starts prematurely. Biochemical and genetic experiments show that PP4c acts by dephosphorylating the microtubule binding protein Ndel1, thereby enabling complex formation with Lis1 to form a functional spindle orientation complex. Our results identify a key regulator of cortical development and demonstrate that changes in the orientation of progenitor division are responsible for the transition between symmetric and asymmetric cell division. PP4c is required for spindle orientation in cortical progenitors Loss of PP4c leads to premature neuronal differentiation Spindle misorientation causes layering defects during a critical time window PP4c acts on Ndel1 and Lis1 Xie et al. address the importance of spindle orientation during cortical development. They show that horizontal spindle orientation is required during a distinct time window at the onset of neurogenesis to ensure symmetric division and maintain the progenitor pool.
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影响因子：
16.2
作者：
Bultje, Ronald S.;Castaneda-Castellanos, David R.;Jan, Lily Yen;Jan, Yuh-Nung;Kriegstein, Arnold R.;Shi, Song-Hai
通讯作者：
Shi, Song-Hai
影响因子：
21.3
作者：
Gruber, Ralph;Zhou, Zhongwei;Wang, Zhao-Qi
通讯作者：
Wang, Zhao-Qi
影响因子：
25
作者：
Gauthier-Fisher, Andree;Lin, Dan C.;Miller, Freda D.
通讯作者：
Miller, Freda D.
影响因子：
2.7
作者：
Hartfuss, E;Galli, R;Götz, M
通讯作者：
Götz, M
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