LIMK1 and LIMK2 regulate cortical development through affecting neural progenitor cell proliferation and migration
LIMK1 and LIMK2 regulate cortical development through affecting neural progenitor cell proliferation and migration
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LIMK1 和 LIMK2 通过影响神经祖细胞增殖和迁移来调节皮质发育
DOI：
10.1186/s13041-019-0487-7
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发表时间：
2019
期刊：
影响因子：
3.6
通讯作者：
Jia Zhengping
中科院分区：
文献类型：
--
作者：
Mao Rui;Deng Rui;Wei Yan;Han Lifang;Meng Yanghong;Xie Wei;Jia Zhengping
LIMK1 和 LIMK2 是介导 Rho 家族小 GTP 酶和 p21 激活激酶 (PAK) 在肌动蛋白细胞骨架调节中的作用的关键下游靶标。 LIMK 对于突触传递、可塑性和记忆形成也至关重要。 LIMK 信号传导的变化与多种神经发育和神经退行性疾病有关，包括自闭症、智力障碍和阿尔茨海默病。然而，LIMK 信号在大脑发育中的作用仍然未知。在本研究中，我们使用 LIMK1 KO 和 LIMK2 KO 小鼠来研究 LIMK 信号在大脑皮层发育中的作用。我们发现这些 KO 小鼠的上皮质层锥体神经元数量减少，并且这种减少伴随着神经祖细胞池的减少和神经元迁移受损。这些结果与在 PAK1 KO 小鼠中发现的结果相似，表明 LIMK 依赖性肌动蛋白调节可能在介导 PAK1 和 Rho 信号传导在皮质发育调节中的作用中发挥关键作用。
LIMK1 and LIMK2 are key downstream targets to mediate the effects of the Rho family small GTPases and p21-activated kinases (PAK) in the regulation of the actin cytoskeleton. LIMKs are also critical for synaptic transmission, plasticity and memory formation. Changes in LIMK signaling are associated with several neurodevelopmental and neurodegenerative diseases, including autism, intellectual disability and Alzheimer’s disease. However, the role of LIMK signaling in brain development remains unknown. In this study, we used LIMK1 KO and LIMK2 KO mice to investigate the role of LIMK signaling in the cerebral cortical development. We found that these KO mice are reduced in the number of pyramidal neurons in upper cortical layers and this reduction is accompanied by a smaller pool of neural progenitor cells and impaired neuronal migration. These results are similar to those found in PAK1 KO mice and suggest that LIMK-dependent actin regulation may play a key role in mediating the effects of PAK1 and Rho signaling in the regulation of cortical development.