Ttc21b Is Required in Bergmann Glia for Proper Granule Cell Radial Migration
Ttc21b Is Required in Bergmann Glia for Proper Granule Cell Radial Migration
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DOI：
10.3390/jdb5040018
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发表时间：
2017-12-01
影响因子：
2.7
通讯作者：
Stottmann, Rolf W.
中科院分区：
文献类型：
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作者：
Driver, Ashley M.;Shumrick, Christopher;Stottmann, Rolf W.
小脑的正常发育依赖于严格调控的增殖、迁移和分化事件。其中任何一种的破坏都会导致从共济失调到儿童肿瘤的一系列小脑表型。动物模型表明，适当调节音猬（Shh）信号对于正常的小脑结构至关重要，而信号的增加导致小脑肿瘤的形成。已知初级纤毛是多种发育信号通路的适当调节所必需的，包括Shh。四肽重复结构域21B （Ttc21b）是正常的初级纤毛形态和功能所必需的，并且主要被认为限制Shh信号。在这里，我们研究了Ttc21b在小脑发育中的作用。令人惊讶的是，伯格曼胶质细胞的Ttc21b消融导致小脑下叶/后叶异位颗粒细胞的积累和Shh信号的减少。Ttc21b消融仅在浦肯野细胞中导致类似的表型，在较少的细胞中看到，但在整个小脑范围内。这些结果表明Ttc21b的表达是发育中的小脑伯格曼胶质细胞结构和信号传递所必需的，并且在某些情况下，Ttc21b的表达增强而不是减弱Shh信号。
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 sonic hedgehog (Shh) 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 Shh. Tetratricopeptide Repeat Domain 21B (Ttc21b) is required for proper primary cilia form and function, and is primarily thought to restrict Shh signaling. Here we investigated a role for Ttc21b in cerebellar development. Surprisingly, Ttc21b ablation in Bergmann glia resulted in the accumulation of ectopic granule cells in the lower/posterior lobes of the cerebellum and a reduction in Shh signaling. Ttc21b 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 Ttc21b expression is required for Bergmann glia structure and signaling in the developing cerebellum, and in some contexts, augments rather than attenuates Shh signaling.