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.
Bibliographical noteKAUST Repository Item: Exported on 2022-05-31
Acknowledgements: This study was funded by grants from the University Research Board (URB) at the American University of Beirut (AUB) and the Lebanese National Council for Scientific Research (LNCSR) to N.G. Part of this study was performed using common equipment and material available at the Kamal A. Shair Central Research Science Laboratory (KAS CRSL) at AUB. R.V. was supported by fellowships from the Vision 2010 strategic plan of the University of Ottawa, the Alzheimer Society of Canada, the Heart and Stroke Foundation of Canada, and, by travel awards from the Léon Fredericq Funds (University Hospital of Liège, Liège, Belgium) and Wallonie-Bruxelles International. We thank Dr. Ruth Slack and Dr. Mireille Kacho at the University of Ottawa for their critical review of the study. We thank also Dr. Raya Saab and Dr. Hassan Zalzali at AUB for their technical assistance. R.V. is currently a postdoctoral researcher at the Belgian Fund for Scientific Research (F.R.S-F.N.R.S.) and R.N. a PhD student in the division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, KSA. M.B. is research assistant in the Department of Neuroscience, Erasmus Medical Center, Rotterdam, The Netherlands.
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