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Publication : Adult neurogenesis requires Smad4-mediated bone morphogenic protein signaling in stem cells.

First Author  Colak D Year  2008
Journal  J Neurosci Volume  28
Issue  2 Pages  434-46
PubMed ID  18184786 Mgi Jnum  J:131092
Mgi Id  MGI:3772959 Doi  10.1523/JNEUROSCI.4374-07.2008
Citation  Colak D, et al. (2008) Adult neurogenesis requires Smad4-mediated bone morphogenic protein signaling in stem cells. J Neurosci 28(2):434-46
abstractText  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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