The contribution of in vivo manipulation of gene expression to the understanding of the function of glypicans.

The name glypican identifies a family of heparan sulfate proteoglycans that are linked to the cell surface by a glycosylphosphatidylinositol anchor. Members of this family have been identified in Drosophila, zebrafish, and mammals. The interest in the study of glypicans has increased in the last few years as a result of the discovery that the glypican-3 gene (GPC-3) is mutated in an overgrowth and dysmorphic syndrome. Despite the increased interest, our knowledge about the function of glypicans is still limited, since the molecular basis for the role of glypican-3 in the regulation of body size remains unknown. The in vivo manipulation of glypican expression in lower organisms, however, has demonstrated that these proteoglycans can modulate cellular responses to Wnts and bone morphogenetic factors. Future studies should investigate whether the phenotype of GPC-3-deficient individuals is also due to altered modulation of cellular responses to these factors.