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Signaling through BMPR-IA regulates quiescence and long-term activity of neural stem cells in the adult hippocampus.

TitleSignaling through BMPR-IA regulates quiescence and long-term activity of neural stem cells in the adult hippocampus.
Publication TypeJournal Article
Year of Publication2010
AuthorsMira H, Andreu Z, Suh H, D Lie C, Jessberger S, Consiglio A, San Emeterio J, Hortigüela R, M Marqués-Torrejón Á, Nakashima K, Colak D, Götz M, Fariñas I, Gage FH
JournalCell Stem Cell
Date Published2010 Jul 2
KeywordsAnimals, Bone Morphogenetic Protein Receptors, Type I, Carrier Proteins, Cell Cycle, Cell Line, Cells, Cultured, Flow Cytometry, Genetic Vectors, Hippocampus, Humans, Lentivirus, Mice, Models, Biological, Neurons, Rats, Rats, Inbred F344, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Smad4 Protein, Stem Cells

Neural 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.

Alternate JournalCell Stem Cell
PubMed ID20621052
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