EXPRESSION OF THE CELL-SURFACE PROTEOGLYCAN GLYPICAN-5 IS DEVELOPMENTALLY-REGULATED IN KIDNEY, LIMB, AND BRAIN

Heparan sulfate is ubiquitous at the cell surface, where it is express ed predominantly on proteoglycans of either the transmembrane syndecan family or the glycosylphosphatidylinositol (GPI)-anchored glypican fa mily, and has been propos ed to function as a ''coreceptor'' for a num ber of ''heparin-binding'' growth factors. Although little is known ab out functional differences between individual members of the glypican gene family, mutations in both the Drosophila gene daily and the human gene for glypican-3 strongly suggest that at least some glypicans do function in cellular growth control and morphogenesis. In particular, deletion of the human glypican-3 gene is responsible for Simpson-Golab i-Behmel syndrome, and its associated pre-and postnatal tissue overgro wth, increased risk of embryonal tumors during early childhood, and nu merous visceral and skeletal anomalies. We have identified and charact erized, by sequencing of EST clones and products of rapid amplificatio n of cDNA ends (RACE), an mRNA that encodes a 572-amino-acid member of the glypican gene family (glypican-5) that is most related (50% amino acid similarity, 39% identity) to glypican-3. Glypican-5 mRNA is dete cted as a 3.9- and 4.4-kb transcript in adult and neonatal mouse brain total RNA, and in situ hybridization results localize transcript prim arily to restricted regions of the developing central nervous system, limb, and kidney in patterns consistent with a role in the control of cell growth or differentiation. Interestingly, glypican-5 localizes to 13q31-32 of the human genome, deletions of which are associated with human 13q-syndrome, a developmental disorder with a pattern of defects that shows significant overlap with the pattern of glypican-5 express ion. (C) 1997 Academic Press.