In vitro differentiation of neural progenitor cells from prenatal rat brain: Common cell surface glycoprotein on three glial cell subsets

Abstract

Glial progenitor cell differentiation and cell lineage relationships during brain development are complex hierarchical processes depending on genetic programming, cell‐cell interactions, and microenvironmental factors. The identification of precursor cell‐specific antigens provides a tool for the study of both normal development and deviations from lineage‐specific differentiation associated with malignant transformation. Monoclonal antibody (mAb) RB13‐6 recognizes a 130‐kDa cell surface glycoprotein (gp130^RB13‐6) expressed by a subset of ⁹OAcGD3‐positive glial precursor cells scattered in the rat neuroepithelium on prenatal day (PRD) 13. During prenatal development the fraction of gp130^RB13‐6‐positive fetal brain cells (FBC) decreased from about 18% (PRD 14) to about 1.5% (PRD 22), coinciding with increasing fractions of more mature cell types, as indicated by the elevated expression of p24^RB21‐15, another cell surface determinant specified by mAb RB21‐15 (Kindler‐Röhrborn et al.; Differentiation 30:53–60, 1985) and other neural cell type‐specific markers. Accordingly, gp130^RB13‐6‐positive precursor cells were localized in the ventricular zones throughout brain development. Concomitant with their formation and in the adult rat brain, ependymal layers lining the ventricular surface, choroid plexus, and the leptomeninges were intensely labeled by anti‐gp130^RB13‐6 mAb. As visualized by confocal laser scanning microscopy of FBC cultures from PRD 13, gp130^RB13‐6 was coexpressed with the RC1 antigen by progenitor cells morphologically resembling radial glia cells. In addition, a very small subpopulation of astrocytes coexpressing gp130^RB13‐6 and glial fibrillary acidic protein (GFAP; RB13‐6 and GFAP (∼25% of all gp130^RB13‐6 expressing cells), apparently generated from gp130^RB13‐6‐positive precursors. Corresponding to in vivo conditions, ciliated ependymal cells but also microglial cells/macrophages and leptomeningeal cells showed strong expression of gp130^RB13‐6 in culture. We thus present a new glycoprotein on the cell surfaces of a glial progenitor cell subset for further studies of cell lineage relationships between radial glia cells, astrocytes, and ependymal cells. J. Neurosci. Res. 48:95–111, 1997.