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TISSUE-SPECIFIC STEM CELLS

BM88/Cend1 Expression Levels Are Critical for Proliferation and Differentiation of Subventricular Zone-Derived Neural Precursor Cells

^aLaboratory of Cellular and Molecular Neurobiology, Hellenic Pasteur Institute, Athens, Greece;
^bGroup of Molecular Virology and Vectorology, Institut Pasteur Paris, Paris, France;
^cLaboratory for Perception and Memory, Institut Pasteur Paris, Centre National de la Recherche Scientifique Unité de Recherche Associée 2182, Paris, France

Key Words. Adult neurogenesis • Neurospheres • Lentiviral vectors • RNA interference • Subventricular zone explants

Correspondence: Dimitra Thomaidou, Ph.D., Laboratory of Cellular and Molecular Neurobiology, Hellenic Pasteur Institute, 127 Vassilissis Sofias Avenue, Athens 115 21, Greece. Telephone: 30-210-64-78-833; Fax: 30-210-64-78-833; e-mail: thomaidou{at}pasteur.gr

Received November 2, 2007; accepted for publication May 13, 2008.
First published online in STEM CELLS EXPRESS   May 22, 2008.

Neural stem cells remain in two areas of the adult mammalian brain, the subventricular zone (SVZ) and the dentate gyrus of the hippocampus. Ongoing neurogenesis via the SVZ-rostral migratory stream pathway maintains neuronal replacement in the olfactory bulb (OB) throughout life. The mechanisms determining how neurogenesis is restricted to only a few regions in the adult, in contrast to its more widespread location during embryogenesis, largely depend on controlling the balance between precursor cell proliferation and differentiation. BM88/Cend1 is a neuronal lineage-specific regulator implicated in cell cycle exit and differentiation of precursor cells in the embryonic neural tube. Here we investigated its role in postnatal neurogenesis. Study of in vivo BM88/Cend1 distribution revealed that it is expressed in low levels in neuronal precursors of the adult SVZ and in high levels in postmitotic OB interneurons. To assess the functional significance of BM88/Cend1 in neuronal lineage progression postnatally, we challenged its expression levels by gain- and loss-of-function approaches using lentiviral gene transfer in SVZ-derived neurospheres. We found that BM88/Cend1 overexpression decreases proliferation and favors neuronal differentiation, whereas its downregulation using new-generation RNA interference vectors yields an opposite phenotype. Our results demonstrate that BM88/Cend1 participates in cell cycle control and neuronal differentiation mechanisms during neonatal SVZ neurogenesis and becomes crucial for the transition from neuroblasts to mature neurons when reaching high levels.

Disclosure of potential conflicts of interest is found at the end of this article.