Li Jiwen, Godoy Marlesa I, Zhang Alice J, Diamante Graciel, Ahn In Sook, Cebrian-Silla Arantxa, Alvarez-Buylla Arturo, Yang Xia, Novitch Bennett G, Zhang Ye
Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at the University of California, Los Angeles (UCLA), USA.
Department of Integrative Biology and Physiology, UCLA.
bioRxiv. 2023 Feb 14:2023.02.14.528567. doi: 10.1101/2023.02.14.528567.
Embryonic neural stem cells (NSCs, , radial glia) in the ventricular-subventricular zone (V-SVZ) generate the majority of neurons and glia in the forebrain. Postnatally, embryonic radial glia disappear and a subpopulation of radial glia transition into adult NSCs. As this transition occurs, widespread neurogenesis in brain regions such as the cerebral cortex ends. The mechanisms that regulate the postnatal disappearance of radial glia and the ending of embryonic neurogenesis remain poorly understood. Here, we show that PR domain-containing 16 (Prdm16) promotes the disappearance of radial glia and the ending of neurogenesis in the cerebral cortex. Genetic deletion of from NSCs leads to the persistence of radial glia in the adult V-SVZ and prolonged postnatal cortical neurogenesis. Mechanistically, Prdm16 induces the postnatal reduction in Vascular Cell Adhesion Molecule 1 (Vcam1). The postnatal disappearance of radial glia and the ending of cortical neurogenesis occur normally in double conditional knockout mice. These observations reveal novel molecular regulators of the postnatal disappearance of radial glia and the ending of embryonic neurogenesis, filling a key knowledge gap in NSC biology.
脑室下区（V-SVZ）的胚胎神经干细胞（NSCs，即放射状胶质细胞）产生前脑的大部分神经元和神经胶质细胞。出生后，胚胎放射状胶质细胞消失，一部分放射状胶质细胞转变为成年神经干细胞。随着这种转变的发生，大脑皮质等脑区广泛的神经发生结束。调节放射状胶质细胞出生后消失和胚胎神经发生结束的机制仍知之甚少。在这里，我们表明含PR结构域16（Prdm16）促进放射状胶质细胞的消失和大脑皮质神经发生的结束。神经干细胞中Prdm16的基因缺失导致成年V-SVZ中放射状胶质细胞持续存在，并延长出生后皮质神经发生。从机制上讲，Prdm16诱导出生后血管细胞黏附分子1（Vcam1）减少。在Prdm16和Vcam1双条件敲除小鼠中，放射状胶质细胞出生后消失和皮质神经发生结束正常发生。这些观察结果揭示了放射状胶质细胞出生后消失和胚胎神经发生结束的新分子调节因子，填补了神经干细胞生物学中的一个关键知识空白。
