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Bmp7 调控了小鼠皮质发生过程中神经祖细胞的存活、增殖和神经发生特性。

Bmp7 regulates the survival, proliferation, and neurogenic properties of neural progenitor cells during corticogenesis in the mouse.

机构信息

Institute of Immunology, Biomedical Sciences Research Center Alexander Fleming, Vari, Hellas-Greece.

出版信息

PLoS One. 2012;7(3):e34088. doi: 10.1371/journal.pone.0034088. Epub 2012 Mar 26.

Abstract

Bone morphogenetic proteins (BMPs) are considered important regulators of neural development. However, results mainly from a wide set of in vitro gain-of-function experiments are conflicting since these show that BMPs can act either as inhibitors or promoters of neurogenesis. Here, we report a specific and non-redundant role for BMP7 in cortical neurogenesis in vivo using knockout mice. Bmp7 is produced in regions adjacent to the developing cortex; the hem, meninges, and choroid plexus, and can be detected in the cerebrospinal fluid. Bmp7 deletion results in reduced cortical thickening, impaired neurogenesis, and loss of radial glia attachment to the meninges. Subsequent in vitro analyses of E14.5 cortical cells revealed that lack of Bmp7 affects neural progenitor cells, evidenced by their reduced proliferation, survival and self-renewal capacity. Addition of BMP7 was able to rescue these proliferation and survival defects. In addition, at the developmental stage E14.5 Bmp7 was also required to maintain Ngn2 expression in the subventricular zone. These data demonstrate a novel role for Bmp7 in the embryonic mouse cortex: Bmp7 nurtures radial glia cells and regulates fundamental properties of neural progenitor cells that subsequently affect Ngn2-dependent neurogenesis.

摘要

骨形态发生蛋白(BMPs)被认为是神经发育的重要调节因子。然而,主要来自广泛的体外功能获得实验的结果相互矛盾,因为这些结果表明 BMPs 可以作为神经发生的抑制剂或促进剂。在这里,我们使用基因敲除小鼠报告了 BMP7 在体内皮质神经发生中的特异性和非冗余作用。Bmp7 在发育中的皮质相邻区域产生,hem、脑膜和脉络丛中均可检测到。Bmp7 的缺失导致皮质增厚减少、神经发生受损以及放射状胶质与脑膜的附着丧失。随后对 E14.5 皮质细胞的体外分析表明,缺乏 Bmp7 影响神经祖细胞,证据是它们的增殖、存活和自我更新能力降低。添加 BMP7 能够挽救这些增殖和存活缺陷。此外,在 E14.5 发育阶段,Bmp7 还需要维持脑室下区 Ngn2 的表达。这些数据表明 Bmp7 在胚胎期小鼠皮质中具有新的作用:Bmp7 滋养放射状胶质细胞,并调节神经祖细胞的基本特性,随后影响依赖 Ngn2 的神经发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73f9/3312908/50b5bae078fc/pone.0034088.g001.jpg

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