Increased neurogenesis in adult mCD24-deficient mice.
mCD24, a glycosylphosphatidylinositol-anchored highly glycosylated molecule, is expressed on differentiating neurons during development. In the adult CNS, its expression is restricted to immature neurons located in two regions showing ongoing neurogenesis: the subventricular zone (SVZ) of the lateral ventricle pathway and the dentate gyrus (DG) of the hippocampal formation. Here, combining bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen labelings we confirmed that mCD24 is expressed on proliferating cells. To determine whether the inactivation of the molecule may affect adult neurogenesis, we analyzed the phenotype of mCD24-deficient mice (mCD24-/-). We labeled cells in S-phase with a pulse, a long, or a cumulative administration of BrdU and analyzed cells in different zones according to their dividing rate (rapid and slow) both in the control and mCD24-/-. We found a significant increase in the number of rapid (in the SVZ and the DG) and slow (in the SVZ) proliferating cells. Cumulative assays revealed a global reduction of the total cell cycle duration of rapidly proliferating precursors of SVZ. We investigated the fate of supernumerary cells and observed an increased number of apoptotic cells (terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling) in the mutant SVZ. Furthermore, we found no difference in the size of the olfactory bulb between wild-type (WT) and mutant mice. In support, mCD24 deletion did not appear to affect migration in the migratory stream. A comparison of the organization of migrating precursors between WT and mCD24 -/-, both in vivo at the optic and electron microscopic levels and in SVZ cultured explants, did not show any changes in the arrangement of neuroblasts in chain-like structures. Altogether, our data suggest that mCD24 regulates negatively cell proliferation in zones of secondary neurogenesis.
Belvindrah
Richard
R
Neurogenèse et Morphogenèse dans le développement et chez l'adulte/Institut de Biologie du Développement de Marseille, Centre National de la Recherche Scientifique, Université de la Méditerranée, Campus de Luminy, 13288 Marseille, France.
Rougon
Geneviève
G
Chazal
Geneviève
G
D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis; D001973:Bromodeoxyuridine / Q000493:pharmacokinetics; D051927:CD24 Antigen; D002452:Cell Count; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D020547:Lateral Ventricles / Q000166:cytology / Q000378:metabolism; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D009830:Olfactory Bulb / Q000166:cytology; D010641:Phenotype; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D013234:Stem Cells / Q000166:cytology
D015703:Antigens, CD; D051927:CD24 Antigen; C497890:Cd24a protein, mouse; D008562:Membrane Glycoproteins; D018809:Proliferating Cell Nuclear Antigen; D001973:Bromodeoxyuridine