IN-VITRO DIFFERENTIATION OF NEURAL PROGENITOR CELLS FROM PRENATAL RAT-BRAIN - COMMON CELL-SURFACE GLYCOPROTEIN ON 3 GLIAL-CELL SUBSETS

Glial progenitor cell differentiation and cell lineage relationships d uring brain development are complex hierarchical processes depending o n genetic programming, cell-cell interactions, and microenvironmental factors. The identification of precursor cell-specific antigens provid es a tool for the study of both normal development and deviations from lineage-specific differentiation associated with malignant transforma tion. Monoclonal antibody (mAb) RB13-6 recognizes a 130-kDa cell surfa ce glycoprotein (gp130(RB13-6)) expressed by a subset of (9)OAcGD3-pos itive glial precursor cells scattered in the rat neuroepithelium on pr enatal day (PRD) 13. During prenatal development the fraction of gp130 (RB13-6)-positive fetal brain cells (FBC) decreased from about 18% (PR D 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-Rohrborn et al.; Differentiation 30:53-60, 1985) and other neu ral cell type-specific markers. Accordingly, gp130(RB13-6)-positive pr ecursor cells were localized in the ventricular zones throughout brain development. Concomitant with their formation and in the adult rat br ain, 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 pro genitor cells morphologically resembling radial glia cells. In additio n, a very small subpopulation of astrocytes coexpressing gp130(RB13-6) and glial fibrillary acidic protein (GFAP; <5%) occurred 3 days after seeding. Primary FBC cultures from PRD 18 contained an increased subs et of astrocytes coexpressing gp130(RB13-6) and GFAP (similar to 25% o f all gp130(RB13-6) expressing cells), apparently generated from gp130 (RB13-6)-positive precursors. Corresponding to in vivo conditions, cil iated ependymal cells but also microglial cells/macrophages and leptom eningeal cells showed strong expression of gp130(RB13-6) in culture. W e thus present a new glycoprotein on the cell surfaces of a glial prog enitor cell subset for further studies of cell lineage relationships b etween radial glia cells, astrocytes, and ependymal cells. (C) 1997 Wi ley-Liss, Inc.