Role of the Retinoblastoma protein, Rb, during adult neurogenesis in the olfactory bulb

• Published in: Scientific reports 2016-02, Vol.6 (1), p.20230-20230, Article 20230
• Main Authors: Naser, Rayan, Vandenbosch, Renaud, Omais, Saad, Hayek, Dayana, Jaafar, Carine, Al Lafi, Sawsan, Saliba, Afaf, Baghdadi, Maarouf, Skaf, Larissa, Ghanem, Noël
• Format: Article
• Language: English
• Subjects: 13/1; 13/100; 13/106; 13/51; 14/19; 38/71; 38/77; 45/29; 631/378/368/2431; 64/60; 692/4017; Animals; Antineoplastic Agents, Hormonal - pharmacology; Apoptosis; Biochemistry, biophysics & molecular biology; Biochimie, biophysique & biologie moléculaire; Brain injury; Cancer; Cell cycle; Cell Differentiation - drug effects; Cell Proliferation; Cell self-renewal; Clonal deletion; Homeodomain Proteins - metabolism; Humanities and Social Sciences; In Situ Hybridization, Fluorescence; Interneurons; Life sciences; Mice; Mice, Transgenic; Microscopy, Fluorescence; Molecular modelling; multidisciplinary; Neural stem cells; Neural Stem Cells - cytology; Neural Stem Cells - metabolism; Neuroblasts; Neurogenesis; Neurogenesis - drug effects; Neurons - metabolism; Olfactory bulb; Olfactory Bulb - cytology; Olfactory Bulb - metabolism; Plasmids - genetics; Plasmids - metabolism; Regeneration; Retina; Retinoblastoma; Retinoblastoma protein; Retinoblastoma Protein - genetics; Retinoblastoma Protein - metabolism; Science; Sciences du vivant; Stem cells; Subventricular zone; Survival; Tamoxifen - pharmacology; Transcription Factors - metabolism; Tumors; γ-Aminobutyric acid
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep20230

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.