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成纤维细胞生长因子 10 是小鼠下丘脑中出生后神经发生的负调节剂。

Fibroblast growth factor 10 is a negative regulator of postnatal neurogenesis in the mouse hypothalamus.

机构信息

School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK.

Institute of Biotechnology, University of Helsinki, Viikinkaari 9, Helsinki 00014, Finland.

出版信息

Development. 2020 Jul 13;147(13):dev180950. doi: 10.1242/dev.180950.

Abstract

New neurons are generated in the postnatal rodent hypothalamus, with a subset of tanycytes in the third ventricular (3V) wall serving as neural stem/progenitor cells. However, the precise stem cell niche organization, the intermediate steps and the endogenous regulators of postnatal hypothalamic neurogenesis remain elusive. Quantitative lineage-tracing revealed that conditional deletion of fibroblast growth factor 10 (Fgf10) from Fgf10-expressing β-tanycytes at postnatal days (P)4-5 results in the generation of significantly more parenchymal cells by P28, composed mostly of ventromedial and dorsomedial neurons and some glial cells, which persist into adulthood. A closer scrutiny and revealed that the 3V wall is not static and is amenable to cell movements. Furthermore, normally β-tanycytes give rise to parenchymal cells via an intermediate population of α-tanycytes with transient amplifying cell characteristics. Loss of Fgf10 temporarily attenuates the amplification of β-tanycytes but also appears to delay the exit of their α-tanycyte descendants from the germinal 3V wall. Our findings suggest that transience of cells through the α-tanycyte domain is a key feature, and Fgf10 is a negative regulator of postnatal hypothalamic neurogenesis.

摘要

新生神经元可在新生啮齿动物的下丘脑生成,其中第三脑室(3V)壁的一部分室管膜细胞作为神经干细胞/祖细胞。然而,新生下丘脑神经发生的精确干细胞生态位组织、中间步骤和内源性调节因子仍不清楚。定量谱系追踪显示,在出生后第 4-5 天(P)从表达成纤维细胞生长因子 10(Fgf10)的β-室管膜细胞条件性删除 Fgf10,会导致到 P28 时实质细胞的生成显著增加,主要由腹内侧和背内侧神经元和一些神经胶质细胞组成,并持续到成年期。更仔细的观察和揭示了 3V 壁不是静态的,并且可以接受细胞运动。此外,通常情况下,β-室管膜细胞通过具有短暂扩增细胞特征的α-室管膜细胞中间群体产生实质细胞。Fgf10 的缺失暂时减弱了β-室管膜细胞的扩增,但似乎也延迟了它们的α-室管膜细胞后代从生发 3V 壁的退出。我们的发现表明,细胞通过α-室管膜细胞结构域的短暂性是一个关键特征,而 Fgf10 是新生下丘脑神经发生的负调节因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/620e/7375484/847dea8cc0ea/develop-147-180950-g1.jpg

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