Driver Ashley M, Shumrick Christopher, Stottmann Rolf W
Division of Human Genetics, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Division of Developmental Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
J Dev Biol. 2017 Dec 19;5(4):18. doi: 10.3390/jdb5040018.
Proper cerebellar development is dependent on tightly regulated proliferation, migration, and differentiation events. Disruptions in any of these leads to a range of cerebellar phenotypes from ataxia to childhood tumors. Animal models have shown that proper regulation of () signaling is crucial for normal cerebellar architecture, and increased signaling leads to cerebellar tumor formation. Primary cilia are known to be required for the proper regulation of multiple developmental signaling pathways, including . () is required for proper primary cilia form and function, and is primarily thought to restrict signaling. Here we investigated a role for in cerebellar development. Surprisingly, ablation in Bergmann glia resulted in the accumulation of ectopic granule cells in the lower/posterior lobes of the cerebellum and a reduction in signaling. ablation in just Purkinje cells resulted in a similar phenotype seen in fewer cells, but across the entire extent of the cerebellum. These results suggest that expression is required for Bergmann glia structure and signaling in the developing cerebellum, and in some contexts, augments rather than attenuates signaling.
正常的小脑发育依赖于严格调控的增殖、迁移和分化过程。这些过程中任何一个环节受到干扰都会导致从小脑性共济失调到儿童肿瘤等一系列小脑表型。动物模型表明，对（）信号通路的适当调控对于正常的小脑结构至关重要，信号增强会导致小脑肿瘤形成。已知初级纤毛对于包括（）在内的多种发育信号通路的适当调控是必需的。（）对于初级纤毛的正常形态和功能是必需的，并且主要被认为是限制（）信号。在这里，我们研究了（）在小脑发育中的作用。令人惊讶的是，伯格曼胶质细胞中的（）缺失导致小脑下叶/后叶中异位颗粒细胞的积累以及（）信号的减少。仅在浦肯野细胞中进行（）缺失会导致在较少细胞中出现类似的表型，但在整个小脑范围内都有。这些结果表明，在发育中的小脑中，伯格曼胶质细胞的结构和信号需要（）表达，并且在某些情况下，会增强而不是减弱（）信号。
