PDK1 Deficit Impairs the Development of the Dentate Gyrus in Mice.

PDK1 Deficit Impairs the Development of the Dentate Gyrus in Mice.
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PDK1 缺陷会损害小鼠齿状回的发育。

DOI:
10.1093/cercor/bhy024
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发表时间:
2018
期刊:
影响因子:
3.7
通讯作者:
Gao Jun
Gao Jun
中科院分区:
医学2区
文献类型:
--
作者:
Xu Min;Han Xiaoning;Liu Rui;Li Yanjun;Qi Cui;Yang Zhongzhou;Zhao Chunjie;Gao Jun

文献摘要

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3-Phosphoinositide-dependent protein kinase-1 (PDK1) is crucial for the development of the dentate gyrus (DG), the first gateway receiving afferent inputs from the entorhinal cortex. However, the role of PDK1 in DG development is unclear. In the present study, by crossingPdk1fl/flmice with theEmx1-creline, we identified that the ablation of PDK1 disrupted the development of DG via decreasing the proliferation, and increasing the differentiation of dentate neural progenitor cells, downregulating AKT activity and upregulating GSK3β signaling. Moreover, PDK1 deletion disrupted the distribution of Reelin+cells and decreased the level ofReelinmRNA which may contribute to the defective migration of progenitor cells and the disrupted radial glial scaffolds. Furthermore, the inhibition of GSK3β activity partially restored the decreased proliferation of primary neural stem cells in vitro. Taken together, our data indicated that the ablation of PDK1 affected the proliferation and differentiation of dentate neural progenitor cells in mice.