Isaksen Toke Jost, Yamashita Toshihide
Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Suita, Japan.
WPI Immunology Frontier Research Center, Osaka University, Suita, Japan.
Neurosci Insights. 2020 Aug 5;15:2633105520948481. doi: 10.1177/2633105520948481. eCollection 2020.
Repulsive guidance molecule A (RGMa) exhibits repulsive guidance of axonal growth and regulates neuronal differentiation during development of the mammalian brain. In this commentary, we describe the findings of our recent paper, "Repulsive Guidance Molecule A Suppresses Adult Neurogenesis," and discuss a possible model for RGMa suppression of newborn neurons that fail to properly migrate into the granular cell layer. In the study, we provided evidence that RGMa suppressed neurite growth and survival of newborn neurons in the adult dentate gyrus. This effect depends on the multifunctional Neogenin receptor expressed in adult neural stem cells through activation of the Rho-associated protein kinase leading to neurite growth inhibition and ultimately cell death. It should be noted that both RGMa and Neogenin interact with several well-described molecules, including bone morphogenetic proteins, that regulate neuronal development. Thus, it is likely that RGMa interacts with other intricate molecular networks that regulate adult neurogenesis.
排斥性导向分子A（RGMa）在哺乳动物大脑发育过程中表现出对轴突生长的排斥性导向作用，并调节神经元分化。在这篇评论中，我们描述了我们最近的论文《排斥性导向分子A抑制成年神经发生》的研究结果，并讨论了RGMa抑制未能正确迁移到颗粒细胞层的新生神经元的一种可能模型。在该研究中，我们提供了证据表明RGMa抑制成年齿状回中新生神经元的神经突生长和存活。这种作用取决于成年神经干细胞中表达的多功能Neogenin受体，通过激活Rho相关蛋白激酶导致神经突生长抑制并最终导致细胞死亡。应该注意的是，RGMa和Neogenin都与几种已被充分描述的分子相互作用，包括调节神经元发育的骨形态发生蛋白。因此，RGMa很可能与其他调节成年神经发生的复杂分子网络相互作用。
