Loss of adenomatous polyposis coli in Bergmann glia disrupts their unique architecture and leads to cell nonautonomous neurodegeneration of cerebellar Purkinje neurons.
Loss of adenomatous polyposis coli in Bergmann glia disrupts their unique architecture and leads to cell nonautonomous neurodegeneration of cerebellar Purkinje neurons.
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DOI：
10.1002/glia.21154
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发表时间：
2011-06
期刊：
影响因子：
6.2
通讯作者：
Fushiki, Shinji
中科院分区：
文献类型：
--
作者：
Wang, Xiaohong;Imura, Tetsuya;Sofroniew, Michael V.;Fushiki, Shinji
The tumor suppressor adenomatous Polyposis Coli (APC) is a multifunctional protein that inhibits the Wnt/beta-catenin signaling pathway and regulates the microtubule and actin cytoskeletons. Using conditional knockout (CKO) mice in which the APC gene is inactivated in glial fibrillary acidic protein (GFAP)-expressing cells, we show a selective and critical role for APC in maintaining the morphology and function of cerebellar Bergmann glia. APC-CKO mice developed Bergmann glia normally until the accumulation of beta-catenin started around postnatal day 10 (P10). Their radial fibers then became shortened with a marked reduction of branching collaterals and their cell bodies translocated into the molecular layer followed by loss of their pial contact and transformation into stellate-shaped cells by P21. Purkinje neurons were normal in appearance and number at P21, but there was significant loss of Purkinje neurons and cerebellar atrophy by middle age. Outside the cerebellum, neither beta-catenin accumulation nor morphological changes were identified in GFAP-expressing astroglia, indicating region-specific effects of APC deletion and an essential role for APC in maintaining the unique morphology of Bergmann glia as compared with other astroglia. These results demonstrate that loss of APC selectively disrupts the Bergmann glial scaffold in late postnatal development and leads to cerebellar degeneration with loss of Purkinje neurons in adults, providing another potential mechanism for region-specific non-cell autonomous neurodegeneration.
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影响因子：
6.2
作者：
Lippman, Jocelyn J.;Lordkipanidze, Tamar;Buell, Margaret E.;Yoon, Sung Ok;Dunaevsky, Anna
通讯作者：
Dunaevsky, Anna
影响因子：
5.2
作者：
Imura, Tetsuya;Wang, Xiaohong;Fushiki, Shinji
通讯作者：
Fushiki, Shinji
影响因子：
50.3
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通讯作者：
Ligon, Keith L.
影响因子：
56.9
作者：
NISHISHO, I;NAKAMURA, Y;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B
影响因子：
56.9
作者：
Lino, M;Goto, K;Ozawa, S
通讯作者：
Ozawa, S