HEPARAN-SULFATE PROTEOGLYCANS ARE REQUIRED FOR MESODERM FORMATION IN XENOPUS-EMBRYOS

Mesoderm forms in the vertebrate embryo as a result of inductive inter actions involving secreted growth factors and cell surface molecules. Proteoglycans have recently been implicated in the control of cell adh esion, migration and growth factor responsiveness. We have found that removal of glycosaminoglycan chains of proteoglycans from Xenopus ecto dermal explants by heparinase, but not by chondroitinase, results in i nhibition of elongation and mesodermal differentiation in response to signaling factors: activin, FGF and Wnt. Heparinase treatment differen tially affected expression of early general and region-specific mesode rmal markers, suggesting that mesodermal cell fates become specified i n the early embryo via at least two signaling pathways which differ in their requirements for heparan sulfate proteoglycans. Addition of sol uble heparan sulfate restored activin-mediated induction of muscle-spe cific actin gene in heparinase-treated explants. Finally, heparinase i nhibited autonomous morphogenetic movements and mesodermal, but not ne ural, differentiation in dorsal marginal zone explants, which normally give rise to mesoderm in the embryo. These results directly demonstra te that heparan sulfate proteoglycans participate in gastrulation and mesoderm formation in the embryo.