Migrational analysis of the constitutively proliferating subependyma population in adult mouse forebrain

Initial experiments to evaluate the in vivo fate(s) of constitutively proli ferating subependymal cells determined that, following in vivo labeling of this population by infection with a retrovirus containing a beta-galactosid ase reporter gene, there was a progressive and eventually complete loss of histochemically beta-galactosidase-positive cells within the lateral ventri cle subependyma with increasing survival times of up to 28 days after retro viral infection. Subsequent experiments were designed to ascertain the pote ntial contributions of: (i) the migration of subependymal cells away from t he forebrain lateral ventricles; and (ii) the downregulation of the retrovi ral reporter gene expression. Retroviral lineage tracing experiments demons trate that a major in vivo fate for constitutively proliferating subependym al cells is their rostral migration away from the walls of the lateral Vent ricle to the olfactory bulb. Although down-regulation of retroviral reporte r gene expression does not contribute to the loss of detection of beta-gala ctosidase-Iabeled cells from the lateral ventricle subependyma, it does res ult in an underestimation of the absolute number of retrovirally labeled ce lls in the olfactory bulb at longer survival times. Furthermore, a temporal decrease in the double labeling of beta-galactosidase-labeled cells with [ H-3]thymidine was observed, indicating that only a subpopulation of the mig ratory subependymal-derived cells continue to actively proliferate en route to the olfactory bulb. These two events may contribute to the lack of a si gnificant increase in the total number of retrovirally labeled subependymal cells during rostral migration. Evidence from separately published studies suggests that cell death is also an important regulator of the size of the constitutively proliferating subependymal population. In summary, in vivo studies utilizing retroviral reporter gene labeling dem onstrate that constitutively proliferating subependymal cells born in the l ateral ventricle migrate rostrally to the olfactory bulb. Loss of prolifera tion potential and retroviral reporter gene down-regulation contribute to t he lack of any significant increase in the total number of labeled cells re covered in the olfactory bulb. (C) 1999 IBRO. Published by Elsevier Science Ltd.