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Adult neurogenesis requires Smad4-mediated bone morphogenic protein signaling in stem cells
被引:205
作者:
Colak, Dilek
[1
]
Mori, Tetsuji
[1
]
Brill, Monika S.
[1
,6
]
Pfeifer, Alexander
[2
]
Falk, Sven
[3
]
Deng, Chuxia
[4
]
Monteiro, Rui
[5
]
Mummery, Christine
[5
]
Sommer, Lukas
[3
]
Goetz, Magdalena
[1
,6
]
机构:
[1] Inst Stem Cell Res, Gesell Strahlung & Unweltforsch, Helmhotz Ctr Munich, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany
[2] Univ Bonn, Inst Pharmacol & Toxicol, D-53113 Bonn, Germany
[3] Univ Zurich, Inst Anat, CH-8057 Zurich, Switzerland
[4] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA
[5] Hubrecht Inst, NL-3584 CT Utrecht, Netherlands
[6] Univ Munich, D-80336 Munich, Germany
关键词:
neural stem cells;
Olig2;
Dlx2;
neurogenesis;
oligodendrocytes;
transplantation;
D O I:
10.1523/JNEUROSCI.4374-07.2008
中图分类号:
Q189 [神经科学];
学科分类号:
071006 ;
摘要:
In the mammalian brain, neurogenesis continues only in few regions of the forebrain. The molecular signals governing neurogenesis in these unique neurogenic niches, however, are still ill defined. Here, we show that bone morphogenic protein (BMP)-mediated signaling is active in adult neural stem cells and is crucial to initiate the neurogenic lineage in the adult mouse subependymal zone. Conditional deletion of Smad4 in adult neural stem cells severely impairs neurogenesis, and this is phenocopied by infusion of Noggin, an extracellular antagonist of BMP. Smad4 deletion in stem, but not progenitor cells, as well as Noggin infusion lead to an increased number of Olig2-expressing progeny that migrate to the corpus callosum and differentiate into oligodendrocytes. Transplantation experiments further verified the cell-autonomous nature of this phenotype. Thus, BMP-mediated signaling via Smad4 is required to initiate neurogenesis from adult neural stem cells and suppress the alternative fate of oligodendrogliogenesis.
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页码:434 / 445
页数:12
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