State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China.
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Stem Cell Reports. 2015 May 12;4(5):795-810. doi: 10.1016/j.stemcr.2015.03.004. Epub 2015 Apr 23.
Metabotropic glutamate receptor 7 (GRM7) has recently been identified to be associated with brain developmental defects, such as attention deficit hyperactivity disorder (ADHD) and autism. However, the function of GRM7 during brain development remains largely unknown. Here, we used gain- and loss-of-function strategies to investigate the role of GRM7 in early cortical development. We demonstrate that Grm7 knockdown increases neural progenitor cell (NPC) proliferation, decreases terminal mitosis and neuronal differentiation, and leads to abnormal neuronal morphology. GRM7 regulates the phosphorylation of cyclic AMP response element-binding protein (CREB) and the expression of Yes-associated protein (YAP) by directly interacting with CaM, which subsequently regulates the expression of CyclinD1 and ultimately affects early cortical development. These defects in neurogenesis are ameliorated by Grm7 overexpression, Creb knockdown, or Yap knockdown. Thus, our findings indicate that GRM7 signaling via CREB and YAP is necessary for neurogenesis in the brain.
代谢型谷氨酸受体 7（GRM7）最近被确定与脑发育缺陷有关，例如注意力缺陷多动障碍（ADHD）和自闭症。然而，GRM7 在大脑发育过程中的功能在很大程度上仍不清楚。在这里，我们使用功能获得和功能丧失策略来研究 GRM7 在早期皮质发育中的作用。我们证明 Grm7 敲低会增加神经祖细胞（NPC）的增殖，减少终末有丝分裂和神经元分化，并导致神经元形态异常。GRM7 通过直接与 CaM 相互作用来调节环磷酸腺苷反应元件结合蛋白（CREB）的磷酸化和 Yes 相关蛋白（YAP）的表达，从而调节细胞周期蛋白 D1 的表达，并最终影响早期皮质发育。通过 Grm7 过表达、Creb 敲低或 Yap 敲低可以改善神经发生缺陷。因此，我们的研究结果表明，GRM7 通过 CREB 和 YAP 的信号传导对于大脑中的神经发生是必要的。
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