Widespread contribution of Gdf7 lineage to cerebellar cell types and implications for hedgehog-driven medulloblastoma formation.
Widespread contribution of Gdf7 lineage to cerebellar cell types and implications for hedgehog-driven medulloblastoma formation.
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DOI：
10.1371/journal.pone.0035541
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Chiang C
中科院分区：
文献类型：
--
作者：
Cheng FY;Huang X;Sarangi A;Ketova T;Cooper MK;Litingtung Y;Chiang C
The roof plate is a specialized embryonic midline tissue of the central nervous system that functions as a signaling center regulating dorsal neural patterning. In the developing hindbrain, roof plate cells express Gdf7 and previous genetic fate mapping studies showed that these cells contribute mostly to non-neural choroid plexus epithelium. We demonstrate here that constitutive activation of the Sonic hedgehog signaling pathway in the Gdf7 lineage invariably leads to medulloblastoma. Lineage tracing analysis reveals that Gdf7-lineage cells not only are a source of choroid plexus epithelial cells, but are also present in the cerebellar rhombic lip and contribute to a subset of cerebellar granule neuron precursors, the presumed cell-of-origin for Sonic hedgehog-driven medulloblastoma. We further show that Gdf7-lineage cells also contribute to multiple neuronal and glial cell types in the cerebellum, including glutamatergic granule neurons, unipolar brush cells, Purkinje neurons, GABAergic interneurons, Bergmann glial cells, and white matter astrocytes. These findings establish hindbrain roof plate as a novel source of diverse neural cell types in the cerebellum that is also susceptible to oncogenic transformation by deregulated Sonic hedgehog signaling.
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DOI：
10.1073/pnas.0910786107
发表时间：
2010-06-08
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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Chizhikov, Victor V.;Lindgren, Anne G.;Millen, Kathleen J.
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通讯作者：
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影响因子：
4.6
作者：
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通讯作者：
Rowitch, DH