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

D Colak, T Mori, MS Brill, A Pfeifer, S Falk… - Journal of …, 2008 - Soc Neuroscience
Journal of Neuroscience, 2008Soc Neuroscience
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 …
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.
Soc Neuroscience