Muñoz Rosana, Moreno Mauricio, Oliva Carlos, Orbenes Claudio, Larraín Juan
Department of Cell and Molecular Biology, Center for Cell Regulation and Pathology, Millennium Nucleus in Developmental Biology, Faculty of Biological Sciences, P. Universidad Católica de Chile, Alameda 340, Santiago, Chile.
Nat Cell Biol. 2006 May;8(5):492-500. doi: 10.1038/ncb1399. Epub 2006 Apr 2.
Early shaping of Xenopus laevis embryos occurs through convergent and extension movements, a process that is driven by intercalation of polarized dorsal mesodermal cells and regulated by non-canonical Wnt signalling. Here, we have identified Xenopus syndecan-4 (xSyn4), a cell-surface transmembrane heparan sulphate proteoglycan. At the gastrula stage, xSyn4 is expressed in the involuting dorsal mesoderm and the anterior neuroectoderm. Later, it is found in the pronephros, branchial arches, brain and tailbud. Both gain- and loss-of-function of xSyn4 impaired convergent extension movements in Xenopus embryos and in activin-treated ectodermal explants. xSyn4 interacts functionally and biochemically with the Wnt receptor Frizzled7 (xFz7) and its signal transducer Dishevelled (xDsh). Furthermore, xSyn4 is necessary and sufficient for translocation of xDsh to the plasma membrane - a landmark in the activation of non-canonical Wnt signalling. Our results suggest that the ability of xSyn4 to translocate xDsh is regulated by fibronectin, a component of the extracellular matrix required for proper convergent extension movements. We propose a model where xSyn4 and fibronectin cooperate with xFz7 and Wnt in the specific activation of the non-canonical Wnt pathway.
非洲爪蟾胚胎的早期形态形成是通过汇聚延伸运动实现的，这一过程由极化的背侧中胚层细胞的插入驱动，并受非经典Wnt信号通路调控。在此，我们鉴定出了非洲爪蟾syndecan-4（xSyn4），一种细胞表面跨膜硫酸乙酰肝素蛋白聚糖。在原肠胚阶段，xSyn4在卷入的背侧中胚层和前神经外胚层中表达。之后，它出现在前肾、鳃弓、脑和尾芽中。xSyn4的功能获得和功能丧失均损害了非洲爪蟾胚胎以及激活素处理的外胚层外植体中的汇聚延伸运动。xSyn4在功能和生化方面与Wnt受体卷曲蛋白7（xFz7）及其信号转导蛋白散乱蛋白（xDsh）相互作用。此外，xSyn4对于xDsh向质膜的转位是必要且充分的，而质膜转位是激活非经典Wnt信号通路的一个标志。我们的结果表明，xSyn4转位xDsh的能力受纤连蛋白调控，纤连蛋白是正常汇聚延伸运动所需的细胞外基质成分。我们提出了一个模型，其中xSyn4和纤连蛋白在非经典Wnt通路的特异性激活中与xFz7和Wnt协同作用。
