Asymmetric centrosome inheritance maintains neural progenitors in the neocortex.

Asymmetric centrosome inheritance maintains neural progenitors in the neocortex.
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DOI:
10.1038/nature08435
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发表时间:
2009-10-15
期刊:
影响因子:
64.8
通讯作者:
--
中科院分区:
综合性期刊1区
文献类型:
--
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放射状胶质祖细胞的不对称分裂在发育中的新皮层的脑室区(VZ)中同时产生自我更新的放射状胶质细胞和分化细胞。当分化细胞离开VZ构成未来的新皮质时,更新的放射状胶质祖细胞留在VZ中进行后续分裂。祖细胞及其分化后代的差异行为对新皮层发育至关重要;然而,确保这些行为差异的机制尚不清楚。在这里,我们表明,不对称中心体遗传调节的差异行为的更新祖细胞和他们的分化后代。放射状胶质祖细胞分裂时中心体复制产生一对具有不同年龄的中心粒的中心体。在神经发生的高峰期,保留老母亲中心粒的中心体留在VZ中,并优先由放射状胶质祖细胞遗传,而包含新母亲中心粒的中心体大多离开VZ,并在很大程度上与分化细胞相关。去除Ninein,一种成熟的中心粒特异性蛋白,破坏了中心体的不对称分离和遗传,并导致VZ的祖细胞过早耗尽。这些结果表明,优先继承的中心体与成熟的老母亲中心粒是需要维持放射状胶质祖细胞在发育中的哺乳动物新皮层。
Asymmetric divisions of radial glial progenitors produce self-renewing radial glia and differentiating cells simultaneously in the ventricular zone (VZ) of the developing neocortex. While differentiating cells leave the VZ to constitute the future neocortex, renewing radial glial progenitors stay in the VZ for subsequent divisions. The differential behaviour of progenitors and their differentiating progeny is essential for neocortical development; however, the mechanisms that ensure these behavioural differences are unclear. Here we show that asymmetric centrosome inheritance regulates the differential behaviour of renewing progenitors and their differentiating progeny. Centrosome duplication in dividing radial glial progenitors generates a pair of centrosomes with differently aged mother centrioles. During peak phases of neurogenesis, the centrosome retaining the old mother centriole stays in the VZ and is preferentially inherited by radial glial progenitors, whereas the centrosome containing the new mother centriole mostly leaves the VZ and is largely associated with differentiating cells. Removal of Ninein, a mature centriole-specific protein, disrupts the asymmetric segregation and inheritance of the centrosome and causes premature depletion of progenitors from the VZ. These results suggest that preferential inheritance of the centrosome with the mature older mother centriole is required for maintaining radial glial progenitors in the developing mammalian neocortex.
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发表时间: 2009-07-30
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影响因子: 16.2
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发表时间: 2009-09-15
期刊: Current biology : CB
影响因子: --
作者:
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通讯作者: Stearns T
DOI: 10.1007/bf00391127
发表时间: 1971-01-01
期刊: ZEITSCHRIFT FUR ZELLFORSCHUNG UND MIKROSKOPISCHE ANATOMIE
影响因子: --
作者:
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通讯作者: RUFFETT, TL