Bone morphogenetic protein dominantly suppresses epidermal growth factor-induced proliferative expansion of adult forebrain neural precursors.

摘要: A single asymmetric division by an adult neural stem cell (NSC) ultimately generates dozens of differentiated progeny, a feat made possible the proliferative expansion transit-amplifying progenitor cells (TAPs). Although NSC activation and TAP is determined pro- anti-proliferative signals found within niche, remarkably little known about how these integrate simultaneous conflicting signals. We investigated this question focusing on subventricular zone (SVZ) niche murine forebrain. Using primary cultures SVZ cells, we demonstrate that Epidermal Growth Factor (EGF) Bone Morphogenetic Protein (BMP)-2 are particularly powerful factors for SVZ-derived precursors. Dose-response experiments showed when simultaneously exposed to both signals, BMP dominantly suppressed EGF-induced proliferation; moreover, dominance extended all parameters precursor behavior tested, including inhibition proliferation, modulation cycle, promotion differentiation, increase death. BMP's effect did not involve mTORC1 or ERK signaling, key mediators had distinct stage-specific consequences, promoting differentiation but quiescence. In line with in vitro data, vivo exogenous limits proliferation TAPs while BMP-SMAD signaling promotes quiescent NSCs. These findings clarify effects BMPs precursors, support hierarchical model which dominate over EGF constitutively drive