Persistent sonic hedgehog signaling in adult brain determines neural stem cell positional identity.

Persistent sonic hedgehog signaling in adult brain determines neural stem cell positional identity.
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DOI:
10.1016/j.neuron.2011.05.018
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发表时间:
2011-07-28
期刊:
影响因子:
16.2
通讯作者:
Alvarez-Buylla A
Alvarez-Buylla A
中科院分区:
医学1区
文献类型:
--
作者:
Ihrie RA;Shah JK;Harwell CC;Levine JH;Guinto CD;Lezameta M;Kriegstein AR;Alvarez-Buylla A

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神经干细胞(Neural Stem Cells,NSCs)存在于成年人大脑的脑室下区(subventricular zone,SVZ)。该区域内的位置决定了神经干细胞产生神经元后代的类型,但成年NSC位置特化的机制仍然未知。我们发现,音刺猬(Shh)信号,导致高gli1水平,发生在腹侧SVZ,并与特定的神经元后代的发生。Shh由一小群腹侧前脑神经元选择性产生。Shh的消融降低了腹侧来源的神经元类型的产生,而背侧神经干细胞中该途径的异位激活将其后代重新指定为深颗粒中间神经元和钙结合蛋白阳性肾小球周围细胞。这些结果表明,Shh是必要的和足够的成人腹侧神经干细胞的规格。
Neural Stem Cells (NSCs) persist in the subventricular zone (SVZ) of the adult brain. Location within this germinal region determines the type of neuronal progeny NSCs generate, but the mechanism of adult NSC positional specification remains unknown. We show that sonic hedgehog (Shh) signaling, resulting in high gli1 levels, occurs in the ventral SVZ and is associated with the genesis of specific neuronal progeny. Shh is selectively produced by a small group of ventral forebrain neurons. Ablation of Shh decreases production of ventrally-derived neuron types, while ectopic activation of this pathway in dorsal NSCs respecifies their progeny to deep granule interneurons and calbindin-positive periglomerular cells. These results show that Shh is necessary and sufficient for the specification of adult ventral NSCs.
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