Glypican-4 is an FGF2-binding heparan sulfate proteoglycan expressed in neural precursor cells

FGF2 is a crucial mitogen for neural precursor cells in the developing cere bral cortex. Heparan sulfate proteoglycans (HSPGs) are thought to play a ro le in cortical neurogenesis by regulating the action of FGF2 on neural prec ursor cells. In this article, we present data indicating that glypican-4 (K -glypican), a GPI-anchored cell surface HSPG, is involved in these processe s. In the developing mouse brain, glypican-4 mRNA is expressed predominantl y in the ventricular zone of the telencephalon, Neither the outer layers of the telencephalic wall nor the ventricular zone of other parts of the deve loping brain express significant levels of glypican-4, with the exception o f the ventricular zone of the tectum. In cultures of E13 rat cortical precu rsor cells, glypican-4 is expressed in cells immunoreactive for nestin and the D1.1 antigen, markers of neural precursor cells. Glypican-4 expression was not detected in early postmitotic or fully differentiated neurons. Reco mbinant glypican-4 produced in immortalized neural precursor cells binds FG F2 through its heparan sulfate chains and suppressed the mitogenic effect o f FGF2 on E13 cortical precursor cells. The spatiotemporal expression patte rn of glypican-4 in the developing cerebral wall significantly overlaps wit h that of FGF2, These results suggest that glypican-4 plays a critical role in the regulation of FGF2 action during cortical neurogenesis, (C) 2000 Wi ley-Liss, Inc.