School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK.
Institute of Biotechnology, University of Helsinki, Viikinkaari 9, Helsinki 00014, Finland.
Development. 2020 Jul 13;147(13):dev180950. doi: 10.1242/dev.180950.
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.
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。