Sonic hedgehog controls stem cell behavior in the postnatal and adult brain
Sonic hedgehog controls stem cell behavior in the postnatal and adult brain
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DOI：
10.1242/dev.01567
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发表时间：
2005-01-01
期刊：
影响因子：
4.6
通讯作者：
Altaba, ARI
中科院分区：
文献类型：
--
作者：
Palma, V;Lim, DA;Altaba, ARI
Sonic hedgehog（Shh）信号控制着个体发育的许多方面，协调一致的生长和模式。在大脑发育过程中，Shh调节早期腹侧模式，而后来它对调节背侧脑中的前体增殖至关重要，即在新皮层，顶盖和小脑中。我们最近发现，Shh还控制了小鼠胚胎新皮层中具有干细胞特性的细胞的行为，另外的研究表明，它与成人腹侧前脑和海马中细胞增殖的控制有关。然而，目前还不清楚它是否以同样的方式调节成体干细胞谱系。类似地，尚不清楚干细胞龛中哪些细胞响应Shh信号。在这里，我们证明，Shh是所需的细胞增殖在小鼠前脑的室管膜下区（SVZ）干细胞龛和新的嗅觉中间神经元在体内的生产。我们鉴定了两个群体的Gli 1（+）Shh信号应答细胞：GFAP（+）SVZ干细胞和GFAP（-）前体细胞。因此，我们发现Shh调节神经球形成干细胞的自我更新，并通过与表皮生长因子（EGF）合作作为有丝分裂原调节SVZ谱系的增殖。总之，我们的数据表明，在成年哺乳动物大脑中的干细胞谱系的调节Shh信号的关键和保守的作用，突出的脑室下干细胞星形胶质细胞和它们的更丰富的衍生前体作为体内目标的Shh信号，并证明了出生后和成年神经发生的Shh信号的要求。
Sonic hedgehog (Shh) signaling controls many; aspects of ontogeny, orchestrating congruent growth and patterning. During brain development, Shh regulates early ventral patterning while later on it is critical for the regulation of precursor proliferation in the dorsal brain, namely in the neocortex, tectum and cerebellum. We have recently shown that Shh also controls the behavior of cells with stem cell properties in the mouse embryonic neocortex, and additional studies have implicated it in the control of cell proliferation in the adult ventral forebrain and in the hippocampus. However, it remains unclear whether it regulates adult stem cell lineages in an equivalent manner. Similarly, it is not known which cells respond to Shh signaling in stem cell niches. Here we demonstrate that Shh is required for cell proliferation in the mouse forebrain's subventricular zone (SVZ) stem cell niche and for the production of new olfactory interneurons in vivo. We identify two populations of Gli1(+) Shh signaling responding cells: GFAP(+) SVZ stem cells and GFAP(-) precursors. Consistently, We show that Shh regulates the self-renewal of neurosphere-forming stem cells and that it modulates proliferation of SVZ lineages by acting as a mitogen in cooperation with epidermal growth factor (EGF). Together, our data demonstrate a critical and conserved role of Shh signaling in the regulation of stem cell lineages in the adult mammalian brain, highlight the subventricular stem cell astrocytes and their more abundant derived precursors as in vivo targets of Shh signaling, and demonstrate the requirement for Shh signaling in postnatal and adult neurogenesis.