School of Biological Sciences, University of East Anglia, Norwich, NR4 7TJ, United Kingdom.
J Neurosci. 2013 Apr 3;33(14):6170-80. doi: 10.1523/JNEUROSCI.2437-12.2013.
Increasing evidence suggests that neurogenesis occurs in the postnatal and adult mammalian hypothalamus. However, the identity and location of the putative progenitor cells is under much debate, and little is known about the dynamics of neurogenesis in unchallenged brain. Previously, we postulated that Fibroblast growth factor 10-expressing (Fgf10(+)) tanycytes constitute a population of progenitor cells in the mouse hypothalamus. Here, we show that Fgf10(+) tanycytes express markers of neural stem/progenitor cells, divide late into postnatal life, and can generate both neurons and astrocytes in vivo. Stage-specific lineage-tracing of Fgf10(+) tanycytes using Fgf10-creERT2 mice, reveals robust neurogenesis at postnatal day 28 (P28), lasting as late as P60. Furthermore, we present evidence for amplification of Fgf10-lineage traced neural cells within the hypothalamic parenchyma itself. The neuronal descendants of Fgf10(+) tanycytes predominantly populate the arcuate nucleus, a subset of which express the orexigenic neuronal marker, Neuropeptide-Y, and respond to fasting and leptin-induced signaling. These studies provide direct evidence in support of hypothalamic neurogenesis during late postnatal and adult life, and identify Fgf10(+) tanycytes as a source of parenchymal neurons with putative roles in appetite and energy balance.
越来越多的证据表明,神经发生发生在产后和成年哺乳动物的下丘脑。然而,假定祖细胞的身份和位置仍存在很大争议,对于未受挑战的大脑中的神经发生动力学知之甚少。以前,我们假设成纤维细胞生长因子 10 表达(Fgf10(+))的室管膜细胞构成了小鼠下丘脑祖细胞的一个群体。在这里,我们表明 Fgf10(+) 室管膜细胞表达神经干细胞/祖细胞的标志物,在出生后晚期分裂,并能在体内产生神经元和星形胶质细胞。使用 Fgf10-creERT2 小鼠对 Fgf10(+) 室管膜细胞进行特定阶段的谱系追踪,揭示了出生后 28 天(P28)强烈的神经发生,持续到 P60。此外,我们还提供了证据表明,在下丘脑实质本身中,Fgf10 谱系追踪的神经细胞会扩增。Fgf10(+) 室管膜细胞的神经元后代主要分布在弓状核中,其中一部分表达食欲素神经元标志物 Neuropeptide-Y,并对禁食和瘦素诱导的信号作出反应。这些研究为产后晚期和成年期下丘脑神经发生提供了直接证据,并确定了 Fgf10(+) 室管膜细胞作为实质神经元的来源,其在食欲和能量平衡中具有潜在作用。