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

Abstract

FGF2 is a crucial mitogen for neural precursor cells in the developing cerebral cortex. Heparan sulfate proteoglycans (HSPGs) are thought to play a role in cortical neurogenesis by regulating the action of FGF2 on neural precursor cells. In this article, we present data indicating that glypican-4 (K-glypican), a GPI-anchored cell surface HSPG, is involved in these processes. In the developing mouse brain, glypican-4 mRNA is expressed predominantly in the ventricular zone of the telencephalon. Neither the outer layers of the telencephalic wall nor the ventricular zone of other parts of the developing brain express significant levels of glypican-4, with the exception of the ventricular zone of the tectum. In cultures of E13 rat cortical precursor 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. Recombinant glypican-4 produced in immortalized neural precursor cells binds FGF2 through its heparan sulfate chains and suppressed the mitogenic effect of FGF2 on E13 cortical precursor cells. The spatiotemporal expression pattern of glypican-4 in the developing cerebral wall significantly overlaps with that of FGF2. These results suggest that glypican-4 plays a critical role in the regulation of FGF2 action during cortical neurogenesis.