Repulsive guidance molecule A (RGMa) is a glycosylphosphatidylinositol-anchored glycoprotein that exhibits repulsive neurite guidance and regulates neuronal differentiation and survival during brain development. However, the function of RGMa in the adult brain is unknown. Here, we show that RGMa is expressed in the adult hippocampus and provide evidence that RGMa signaling suppresses adult neurogenesis. Knockdown of RGMa in the dentate gyrus increased the number of surviving newborn neurons; however, these cells failed to properly migrate into the granular cell layer. In vitro, RGMa stimulation of adult neural stem cells suppressed neurite outgrowth of newborn neurons, which could be prevented by knockdown of the multifunctional receptor neogenin, as well as pharmacological inhibition of the downstream target Rho-associated protein kinase. These findings present a function for RGMa in the adult brain and add to the intricate molecular network that regulates adult brain plasticity.

排斥指导分子A（RGMa）是糖基磷脂酰肌醇固定的糖蛋白，具有排斥性神经突指导，并调节大脑发育过程中的神经元分化和存活。但是，RGMa在成人大脑中的功能尚不清楚。在这里，我们显示RGMa在成人海马中表达，并提供RGMa信号抑制成人神经发生的证据。敲除齿状回中的RGMa可增加存活的新生神经元的数量。但是，这些细胞无法正确迁移到颗粒细胞层中。体外，RGMa刺激成年神经干细胞抑制了新生神经元的神经突生长，这可以通过敲除多功能受体新生蛋白以及下游靶点Rho相关蛋白激酶的药理作用来预防。这些发现为成年大脑中的RGMa发挥了功能，并增加了调节成年大脑可塑性的复杂分子网络。