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The Journal of Neuroscience, May 1, 2002, 22(9):3594-3607
Increased Neurogenesis in Adult mCD24-Deficient Mice
Richard
Belvindrah,
Geneviève
Rougon, and
Geneviève
Chazal
Neurogenèse et Morphogenèse dans le développement et
chez l'adulte/Institut de Biologie du Développement de Marseille,
Centre National de la Recherche Scientifique, Institut National de la
Santé et de la Recherche Médicale, Université de la
Méditerranée, Campus de Luminy, 13288 Marseille, France
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.
Key words:
mCD24; proliferation; adult neurogenesis; neural
progenitor; rostral migratory stream; apoptosis
Copyright © 2002 Society for Neuroscience 0270-6474/02/2293594-14$05.00/0
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