TY - JOUR
T1 - Signaling through BMPR-IA regulates quiescence and long-term activity of neural stem cells in the adult hippocampus
AU - Mira, Helena
AU - Andreu, Zoraida
AU - Suh, Hoonkyo
AU - Chichung Lie, D.
AU - Jessberger, Sebastian
AU - Consiglio, Antonella
AU - Emeterio, Juana San
AU - Hortigüela, Rafael
AU - Marqués-Torrejón, María Ángeles
AU - Nakashima, Kinichi
AU - Colak, Dilek
AU - Götz, Magdalena
AU - Fariñas, Isabel
AU - Gage, Fred H.
N1 - Funding Information:
The authors thank Dr.Yuji Mishina for Bmpr1a flox/flox and Bmpr1a wt/null mice and Dr. C.X. Deng for the Smad4 flox/flox mice. They also thank Mary Lynn Gage for editorial support, Dr. Pilar Sánchez-Gómez for helpful discussions and suggestions, Dr. Mari Paz Rubio, Maria José Palop, André Luis Carvalho, Mireia Moreno, Yolanda Noriega, and Mario Alía for technical assistance. S.J. was supported in part by the Deutsche Forschungsgemeinschaft; H.M. was supported by the Programa Ramon y Cajal from the Spanish Ministerio de Educacion y Ciencia (MEC); Z.A. was supported by the Centro de Investigación Príncipe Felipe; and M.A.M-T. is a recipient of a pre-doctoral fellowship from the FPI/MEC. M.G. was funded by Helma and SFB 596. Additional support was provided by grants from Ministerio de Sanidad y Consumo (MSC; Fondo de Investigación Sanitaria-PI06/0754 and PI09/2254) to H.M.; from MEC (SAF2005-06325), MSC (RETIC Tercel and CIBERNED) and Fundación “la Caixa” to I.F., and from the Bavarian Network on Adult Neural Stem Cells “FORNEUROCELL” to D.C.L.
PY - 2010/7
Y1 - 2010/7
N2 - 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.
AB - 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.
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U2 - 10.1016/j.stem.2010.04.016
DO - 10.1016/j.stem.2010.04.016
M3 - Article
C2 - 20621052
AN - SCOPUS:77957654497
SN - 1934-5909
VL - 7
SP - 78
EP - 89
JO - Cell Stem Cell
JF - Cell Stem Cell
IS - 1
ER -