Heparan sulfate proteoglycans are required for mesoderm formation in Xenopus embryos.
Mesoderm forms in the vertebrate embryo as a result of inductive interactions involving secreted growth factors and cell surface molecules. Proteoglycans have recently been implicated in the control of cell adhesion, migration and growth factor responsiveness. We have found that removal of glycosaminoglycan chains of proteoglycans from Xenopus ectodermal explants by heparinase, but not by chondroitinase, results in inhibition of elongation and mesodermal differentiation in response to signaling factors: activin, FGF and Wnt. Heparinase treatment differentially affected expression of early general and region-specific mesodermal markers, suggesting that mesodermal cell fates become specified in the early embryo via at least two signaling pathways which differ in their requirements for heparan sulfate proteoglycans. Addition of soluble heparan sulfate restored activin-mediated induction of muscle-specific actin gene in heparinase-treated explants. Finally, heparinase inhibited autonomous morphogenetic movements and mesodermal, but not neural, differentiation in dorsal marginal zone explants, which normally give rise to mesoderm in the embryo. These results directly demonstrate that heparan sulfate proteoglycans participate in gastrulation and mesoderm formation in the early embryo.
Itoh
K
K
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA.
Sokol
S Y
SY
D028341:Activins; D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004627:Embryonic Induction / Q000187:drug effects / Q000502:physiology*; D005346:Fibroblast Growth Factors / Q000502:physiology; D005775:Gastrula / Q000502:physiology; D006133:Growth Substances / Q000502:physiology; D006493:Heparin / Q000031:analogs & derivatives* / Q000502:physiology; D019763:Heparin Lyase; D007265:Inhibins / Q000502:physiology; D008648:Mesoderm / Q000187:drug effects / Q000502:physiology*; D009024:Morphogenesis / Q000187:drug effects / Q000502:physiology; D011133:Polysaccharide-Lyases / Q000494:pharmacology; D011509:Proteoglycans / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology*
D006133:Growth Substances; D011509:Proteoglycans; C036090:heparin proteoglycan; D028341:Activins; D007265:Inhibins; D005346:Fibroblast Growth Factors; D006493:Heparin; D011133:Polysaccharide-Lyases; D019763:Heparin Lyase