title: The proapoptotic activities of Bax and Bak limit the size of the neural stem cell pool.
abstract: The proapoptotic Bcl-2 family members Bak and Bax play central and redundant roles in the regulation of apoptosis. In this study, we investigated the effect of loss of Bax and Bak in the CNS. The adult bax-/-bak-/- mice display masses of densely staining cells in the proliferative zones of the brain. These cells are shown to be a mix of neural progenitor cells and postmitotic cells at different stages of neural and glial differentiation. Both neural progenitor cells and mature neurons derived from bax-/-bak-/- mice were resistant to various apoptotic stimuli. Despite this resistance, postmitotic mature bax-/-bak-/- neurons remain as sensitive to excitoxic death as wild-type neurons. Thus, Bax and Bak play a critical role in regulating the number of neural progenitor cells in the adult brain but are not absolutely required for the initiation of neuronal cell death after neurotoxic injury.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Tullia
authors.initials: T
authors.lastname: Lindsten
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Golden
authors.forename: Wei-Xing
authors.initials: WX
authors.lastname: Zong
authors.forename: Jeremy
authors.initials: J
authors.lastname: Minarcik
authors.forename: Marian H
authors.initials: MH
authors.lastname: Harris
authors.forename: Craig B
authors.initials: CB
authors.lastname: Thompson
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D005434:Flow Cytometry; D020547:Lateral Ventricles / Q000166:cytology; D008565:Membrane Proteins / Q000172:deficiency / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000494:pharmacology / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein
chemical_list: D000943:Antigens, Differentiation; C494773:Bak1 protein, mouse; C494827:Bax protein, mouse; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein