Role of the Retinoblastoma protein, Rb, during adult neurogenesis in the olfactory bulb
| Autor: | Rayan Naser, Afaf Saliba, Dayana Hayek, Sawsan M. Al Lafi, Noël Ghanem, Carine Jaafar, Larissa Skaf, Renaud Vandenbosch, Maarouf Baghdadi, Saad Omais |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Antineoplastic Agents Hormonal Rostral migratory stream Neurogenesis Cellular differentiation Subventricular zone Mice Transgenic Retinoblastoma Protein Article Mice 03 medical and health sciences 0302 clinical medicine Neural Stem Cells Neuroblast medicine Animals In Situ Hybridization Fluorescence Cell Proliferation Homeodomain Proteins Neurons Multidisciplinary biology Retinoblastoma protein Cell Differentiation Anatomy Olfactory Bulb Neural stem cell Olfactory bulb Cell biology Tamoxifen 030104 developmental biology medicine.anatomical_structure Microscopy Fluorescence nervous system biology.protein 030217 neurology & neurosurgery Plasmids Transcription Factors |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep20230 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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