Increased Neurogenesis in Adult mCD24-Deficient Mice

Abstract

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 (mCD24Ϫ/Ϫ). 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 mCD24Ϫ/Ϫ. 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 transferasemediated 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 Ϫ/Ϫ, 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.

CD24 is expressed by myofiber synaptic nuclei and regulates synaptic transmission

“…CD24 is indeed expressed in developing neurons and implicated in regulating neuronal proliferation, neuronal migration, and neurite extension (25)(26)(27). Nonetheless, the in vivo role for CD24 in the nervous system is poorly understood (25).…”

Mechanism of stem cells in the central nervous system

“…This issue has been addressed by looking by electron microscopy (EM) at BrdU immunoreactive ependymal cells and indeed they are labeled (Momma et al, 2002). Additionally, in the mCD24 mutant mice, EM is demonstrating that ependymal cells, expressing BrdU and S100b and/or mCD24, do proliferate under physiological conditions and not only after lesion, as has been reported (Johansson et al, 1999b;Namiki and Tator, 1999;Belvindrah et al, 2002;Liu et al, 2002). Moreover, if CNS stem cells were localized in the SVZ it would indicate that there are at least two different types of stem cells in the CNS or that they are randomly distributed.…”

β1 Integrins Control the Formation of Cell Chains in the Adult Rostral Migratory Stream

“…The following antibodies were used: anti-␤1 integrins rabbit polyclonal (Graus-Porta et al, 2001), GFAP rabbit polyclonal (DakoCytomation, Glostrup, Denmark), PSA-NCAM mouse IgM (kindly provided by G. Rougon, Université de la Mediterranée AixMarseille 2, Marseille, France), bromodeoxyuridine (BrdU) mouse IgG (BD Biosciences), laminin rabbit polyclonal (kindly provided by L. Sorokin, University of Uppsala, Uppsala, Sweden), calretinin, polyclonal rabbit (Chemicon, Temecula, CA), caspase 3 polyclonal rabbit (Asp175; Cell Signaling Technology, Beverly, MA). Staining with mouse anti BrdU IgG was performed as described previously (Belvindrah et al, 2002). Mice were administered with BrdU (10 mg/ml in PBS, 50 mg/kg of body weight).…”

“…A total of three Itgb1-CNSko mice and three control littermates were processed. Serial sections were stained with Nissl as described previously (Belvindrah et al, 2002). The surface of the OB was determined using MetaMorph Software (Molecular Devices, Palo Alto, CA).…”