Wechsler-Reya R J, Scott M P
Department of Developmental Biology, Howard Hughes Medical Institute, Stanford University School of Medicine, California 94305, USA.
Neuron. 1999 Jan;22(1):103-14. doi: 10.1016/s0896-6273(00)80682-0.
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.
小脑颗粒细胞是大脑中数量最多的神经元类型，但控制其生成的分子机制尚未完全明确。我们发现，由浦肯野细胞产生的音猬因子（Shh）可调节颗粒细胞前体（GCPs）的分裂。用Shh处理GCPs可防止其分化，并诱导强烈且持久的增殖反应。该反应可被碱性成纤维细胞生长因子或蛋白激酶A的激活所抑制。在体内阻断Shh功能会显著降低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深入见解。
