6533b7d3fe1ef96bd12613cd
RESEARCH PRODUCT
Signaling through BMPR-IA regulates quiescence and long-term activity of neural stem cells in the adult hippocampus.
Magdalena GötzDilek ColakJuana San EmeterioHelena MiraHelena MiraSebastian JessbergerSebastian JessbergerZoraida AndreuZoraida AndreuRafael HortigüelaHoonkyo SuhHoonkyo SuhD. Chichung LieMaría ÁNgeles Marqués-torrejónAntonella ConsiglioIsabel FariñasFred H. GageKinichi NakashimaKinichi Nakashimasubject
medicine.medical_specialtyanimal structuresGenetic VectorsHippocampal formationBiologyBone morphogenetic proteinHippocampusModels BiologicalMOLNEUROCell LineMiceNeural Stem CellsInternal medicineGeneticsmedicineAnimalsHumansNogginBone Morphogenetic Protein Receptors Type ICells Culturedreproductive and urinary physiologySmad4 ProteinNeuronsReverse Transcriptase Polymerase Chain ReactionStem CellsCell CycleLentivirusNeurogenesisCentral-nervous-system; Bone morphogenetic protein; Dentate gyrus; Progenitor cells; Neurogenesis; Expression; Receptor; Noggin; Brain; DifferentiationCell BiologyFlow CytometrySTEMCELLRats Inbred F344BMPR1ANeural stem cellRatsCell biologyEndocrinologyStem cell divisionnervous systemembryonic structuresMolecular MedicineStem cellbiological phenomena cell phenomena and immunityCarrier ProteinsSignal Transductiondescription
SummaryNeural stem cells (NSCs) in the adult hippocampus divide infrequently, and the molecules that modulate their quiescence are largely unknown. Here, we show that bone morphogenetic protein (BMP) signaling is active in hippocampal NSCs, downstream of BMPR-IA. BMPs reversibly diminish proliferation of cultured NSCs while maintaining their undifferentiated state. In vivo, acute blockade of BMP signaling in the hippocampus by intracerebral infusion of Noggin first recruits quiescent NSCs into the cycle and increases neurogenesis; subsequently, it leads to decreased stem cell division and depletion of precursors and newborn neurons. Consistently, selective ablation of Bmpr1a in hippocampal NSCs, or inactivation of BMP canonical signaling in conditional Smad4 knockout mice, transiently enhances proliferation but later leads to a reduced number of precursors, thereby limiting neuronal birth. BMPs are therefore required to balance NSC quiescence/proliferation and to prevent loss of the stem cell activity that supports continuous neurogenesis in the mature hippocampus.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2010-07-01 |