Control of neuronal precursor proliferation in the cerebellum by sonic hedgehog
Control of neuronal precursor proliferation in the cerebellum by sonic hedgehog
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DOI：
10.1016/s0896-6273(00)80682-0
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发表时间：
1999-01-01
期刊：
影响因子：
16.2
通讯作者：
Scott, MP
中科院分区：
文献类型：
--
作者：
Wechsler-Reya, RJ;Scott, MP
小脑颗粒细胞是大脑中最丰富的神经元类型，但控制其产生的分子机制尚不完全清楚。我们发现浦肯野细胞制造的Sonic hedgehog （Shh）调节颗粒细胞前体（GCPs）的分裂。用Shh治疗GCPs可防止分化并诱导有效的、持久的增殖反应。这种反应可以通过碱性成纤维细胞生长因子或蛋白激酶a的激活来抑制。在体内阻断Shh功能可显著减少GCP的增殖。这些发现为小脑正常生长和肿瘤发生的机制提供了见解。
Cerebellar granule cells are the most abundant type of neuron in the brain, but the molecular mechanisms that control their generation are incompletely understood. We show that Sonic hedgehog (Shh), which is made by Purkinje cells, regulates the division of granule cell precursors (GCPs). Treatment of GCPs with Shh prevents differentiation and induces a potent, long-lasting proliferative response. This response can be inhibited by basic fibroblast growth factor or by activation of protein kinase A. Blocking Shh function in vivo dramatically reduces GCP proliferation. These findings provide insight into the mechanisms of normal growth and tumorigenesis in the cerebellum.