Itoh K, Sokol S Y
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA.
Development. 1994 Sep;120(9):2703-11. doi: 10.1242/dev.120.9.2703.
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.
在脊椎动物胚胎中，中胚层的形成是由涉及分泌型生长因子和细胞表面分子的诱导性相互作用导致的。蛋白聚糖最近被认为与细胞黏附、迁移及生长因子反应性的控制有关。我们发现，用肝素酶而非软骨素酶去除非洲爪蟾外胚层外植体中蛋白聚糖的糖胺聚糖链，会导致对外源信号因子（激活素、成纤维细胞生长因子和Wnt）的伸长和中胚层分化受到抑制。肝素酶处理对早期一般中胚层标记物和区域特异性中胚层标记物的表达有不同影响，这表明中胚层细胞命运在早期胚胎中至少通过两条对硫酸乙酰肝素蛋白聚糖需求不同的信号通路得以确定。添加可溶性硫酸乙酰肝素可恢复肝素酶处理的外植体中激活素介导的肌肉特异性肌动蛋白基因诱导。最后，肝素酶抑制了背侧边缘区外植体的自主形态发生运动以及中胚层而非神经的分化，背侧边缘区外植体在胚胎中通常会发育为中胚层。这些结果直接表明硫酸乙酰肝素蛋白聚糖参与了早期胚胎的原肠胚形成和中胚层形成。
