BM88/Cend1 expression levels are critical for proliferation and differentiation of subventricular zone-derived neural precursor cells.
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.
Katsimpardi
Lida
L
Laboratory of Cellular and Molecular Neurobiology, Hellenic Pasteur Institute, 127 Vassilissis Sofias Avenue, Athens 115 21, Greece.
Gaitanou
Maria
M
Malnou
Cecile E
CE
Lledo
Pierre-Marie
PM
Charneau
Pierre
P
Matsas
Rebecca
R
Thomaidou
Dimitra
D
D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D013552:Swine
C496858:Cend1 protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins