title: Role of the Retinoblastoma protein, Rb, during adult neurogenesis in the olfactory bulb.
abstract: Adult neural stem cells (aNSCs) are relatively quiescent populations that give rise to distinct neuronal subtypes throughout life, yet, at a very low rate and restricted differentiation potential. Thus, identifying the molecular mechanisms that control their cellular expansion is critical for regeneration after brain injury. Loss of the Retinoblastoma protein, Rb, leads to several defects in cell cycle as well as neuronal differentiation and migration during brain development. Here, we investigated the role of Rb during adult neurogenesis in the olfactory bulb (OB) by inducing its temporal deletion in aNSCs and progenitors. Loss of Rb was associated with increased proliferation of adult progenitors in the subventricular zone (SVZ) and the rostral migratory stream (RMS) but did not alter self-renewal of aNSCs or neuroblasts subsequent migration and terminal differentiation. Hence, one month after their birth, Rb-null neuroblasts were able to differentiate into distinct subtypes of GABAergic OB interneurons but were gradually lost after 3 months. Similarly, Rb controlled aNSCs/progenitors proliferation in vitro without affecting their differentiation capacity. This enhanced SVZ/OB neurogenesis associated with loss of Rb was only transient and negatively affected by increased apoptosis indicating a critical requirement for Rb in the long-term survival of adult-born OB interneurons.
authors: Department of Biology, American University of Beirut, Lebanon.
authors: Rayan
authors: R
authors: Naser
authors: Department of Cellular and Molecular Medicine, University of Ottawa, Canada.
authors: Renaud
authors: R
authors: Vandenbosch
authors: Department of Biology, American University of Beirut, Lebanon.
authors: Saad
authors: S
authors: Omais
authors: Department of Biology, American University of Beirut, Lebanon.
authors: Dayana
authors: D
authors: Hayek
authors: Department of Biology, American University of Beirut, Lebanon.
authors: Carine
authors: C
authors: Jaafar
authors: Department of Biology, American University of Beirut, Lebanon.
authors: Sawsan
authors: S
authors: Al Lafi
authors: Department of Biology, American University of Beirut, Lebanon.
authors: Afaf
authors: A
authors: Saliba
authors: Department of Biology, American University of Beirut, Lebanon.
authors: Maarouf
authors: M
authors: Baghdadi
authors: Department of Biology, American University of Beirut, Lebanon.
authors: Larissa
authors: L
authors: Skaf
authors: Department of Biology, American University of Beirut, Lebanon.
authors: Noël
authors: N
authors: Ghanem
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation; D018398:Homeodomain Proteins / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000378:metabolism; D009830:Olfactory Bulb / Q000166:cytology* / Q000378:metabolism; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D018931:Antineoplastic Agents, Hormonal; C088334:Distal-less homeobox proteins; C501120:Dlx5 protein, mouse; D018398:Homeodomain Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D013629:Tamoxifen