PAK1 regulates cortical development via promoting neuronal migration and progenitor cell proliferation.
PAK1 regulates cortical development via promoting neuronal migration and progenitor cell proliferation.
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PAK1 通过促进神经元迁移和祖细胞增殖来调节皮质发育。
DOI：
10.1186/s13041-015-0124-z
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发表时间：
2015-06-05
期刊：
影响因子：
3.6
通讯作者：
Jia Z
中科院分区：
文献类型：
--
作者：
Pan X;Chang X;Leung C;Zhou Z;Cao F;Xie W;Jia Z
p21激活激酶1（PAK 1）是一种丝氨酸/苏氨酸激酶，已知被Rho家族小GTP酶激活，并在细胞骨架重组、棘形态和突触可塑性中起关键作用。PAK 1还涉及许多神经发育和神经退行性疾病，包括自闭症，智力残疾和阿尔茨海默病。然而，PAK 1在早期脑发育中的作用仍然未知。在这项研究中，我们采用遗传操作来研究PAK 1在小鼠大脑皮层发育中的作用。我们发现，与野生型同窝小鼠相比，PAK 1基因敲除小鼠大脑皮层几层中锥体神经元的数量减少，这与神经祖细胞池较小和神经元迁移受损有关。这些结果表明，PAK 1通过促进神经祖细胞的增殖和促进这些神经元迁移到皮质的特定区域来调节皮质发育。
p21-activated kinase 1 (PAK1) is a serine/threonine kinase known to be activated by the Rho family small GTPases and to play a key role in cytoskeletal reorganization, spine morphology and synaptic plasticity. PAK1 is also implicated in a number of neurodevelopmental and neurodegenerative diseases, including autism, intellectual disability and Alzheimer’s disease. However, the role of PAK1 in early brain development remains unknown. In this study, we employed genetic manipulations to investigate the role of PAK1 in the cerebral cortical development in mice. We showed that compared to the wild type littermates, PAK1 knockout mice have a reduction in the number of pyramidal neurons in several layers of the cerebral cortex, which is associated with a smaller pool of neural progenitor cells and impaired neuronal migration. These results suggest that PAK1 regulates cortical development by promoting the proliferation of neural progenitor cells and facilitating the migration of these neurons to specific regions of the cortex.
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