TY - JOUR
T1 - Adult neurogenesis requires Smad4-mediated bone morphogenic protein signaling in stem cells.
AU - Colak, D.
AU - Mori, T.
AU - Brill, M.S
AU - Pfeifer, A.
AU - Falk, S.
AU - Deng, C.
AU - Monteiro, R.
AU - Mummery, C.L.
AU - Sommer, L.
AU - Gotz, M.
N1 - Reporting year: 2008
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
U2 - 10.1523/JNEUROSCI.4374-07.2008
DO - 10.1523/JNEUROSCI.4374-07.2008
M3 - Article
SN - 0270-6474
VL - 28
SP - 434
EP - 445
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 2
ER -