Dahmane N, Ruiz i Altaba A
The Skirball Institute, Developmental Genetics Program and Department of Cell Biology, NYU School of Medicine, New York, NY 10016, USA.
Development. 1999 Jun;126(14):3089-100. doi: 10.1242/dev.126.14.3089.
The molecular bases of brain development and CNS malignancies remain poorly understood. Here we show that Sonic hedgehog (Shh) signaling controls the development of the cerebellum at multiple levels. SHH is produced by Purkinje neurons, it is required for the proliferation of granule neuron precursors and it induces the differentiation of Bergmann glia. Blocking SHH function in vivo results in deficient granule neuron and Bergmann glia differentiation as well as in abnormal Purkinje neuron development. Thus, our findings provide a molecular model for the growth and patterning of the cerebellum by SHH through the coordination of the development of cortical cerebellar cell types. In addition, they provide a cellular context for medulloblastomas, childhood cancers of the cerebellum.
大脑发育和中枢神经系统恶性肿瘤的分子基础仍知之甚少。在此我们表明，音猬因子（Shh）信号在多个层面控制小脑的发育。SHH由浦肯野神经元产生，它是颗粒神经元前体细胞增殖所必需的，并且它诱导伯格曼胶质细胞的分化。在体内阻断SHH功能会导致颗粒神经元和伯格曼胶质细胞分化不足以及浦肯野神经元发育异常。因此，我们的研究结果提供了一个分子模型，说明SHH如何通过协调小脑皮质细胞类型的发育来促进小脑的生长和形成模式。此外，这些结果为髓母细胞瘤（一种儿童期小脑癌症）提供了细胞背景。
