title: The autophagy regulators Ambra1 and Beclin 1 are required for adult neurogenesis in the brain subventricular zone.
abstract: Autophagy is a conserved proteolytic mechanism required for maintaining cellular homeostasis. The role of this process in vertebrate neural development is related to metabolic needs and stress responses, even though the importance of its progression has been observed in a number of circumstances, both in embryonic and in postnatal differentiating tissues. Here we show that the proautophagic proteins Ambra1 and Beclin 1, involved in the initial steps of autophagosome formation, are highly expressed in the adult subventricular zone (SVZ), whereas their downregulation in adult neural stem cells in vitro leads to a decrease in cell proliferation, an increase in basal apoptosis and an augmented sensitivity to DNA-damage-induced death. Further, Beclin 1 heterozygosis in vivo results in a significant reduction of proliferating cells and immature neurons in the SVZ, accompanied by a marked increase in apoptotic cell death. In sum, we propose that Ambra1- and Beclin 1-mediated autophagy plays a crucial role in adult neurogenesis, by controlling the survival of neural precursor cells.
authors.affiliation: 1] IRCCS Fondazione Santa Lucia, Rome 00143, Italy [2] Department of Biology, University of Rome Tor Vergata, Rome 00133, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Yazdankhah
authors.affiliation: Institute of Cell Biology and Neurobiology, National Research Council, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Farioli-Vecchioli
authors.affiliation: Research Group in Molecular Developmental Neurobiology, Max-Planck Institute for Biophysical Chemistry, Göttingen 37077, Germany.
authors.forename: A B
authors.initials: AB
authors.lastname: Tonchev
authors.affiliation: Research Group in Molecular Developmental Neurobiology, Max-Planck Institute for Biophysical Chemistry, Göttingen 37077, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Stoykova
authors.affiliation: 1] IRCCS Fondazione Santa Lucia, Rome 00143, Italy [2] Department of Biology, University of Rome Tor Vergata, Rome 00133, Italy [3] Unit of Cell Stress and Survival, Danish Cancer Society Research Center, Copenhagen 2100, Denmark.
authors.forename: F
authors.initials: F
authors.lastname: Cecconi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy; D000071186:Beclin-1; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D006579:Heterozygote; D020547:Lateral Ventricles / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C521754:Ambra1 protein, mouse; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins