Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.
Neuron. 2011 Jul 28;71(2):250-62. doi: 10.1016/j.neuron.2011.05.018.
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.
神经干细胞（NSCs）存在于成年大脑的侧脑室下区（SVZ）中。位置决定了 NSCs 产生的神经元祖细胞的类型，但成年 NSCs 位置指定的机制尚不清楚。我们发现， sonic hedgehog (Shh) 信号转导导致高水平的 gli1 表达发生在 SVZ 的腹侧，与特定神经元祖细胞的产生有关。Shh 由一小群前脑腹侧神经元选择性产生。Shh 的缺失减少了腹侧来源的神经元类型的产生，而该途径在背侧 NSCs 中的异位激活则重新指定了它们的祖细胞为深部颗粒中间神经元和 calbindin 阳性的肾小球旁细胞。这些结果表明，Shh 是成年腹侧 NSCs 特化所必需和充分的。
