Olivares Gonzalo H, Carrasco Héctor, Aroca Francisco, Carvallo Loreto, Segovia Fabián, Larraín Juan
Center for Aging and Regeneration, Center for Cell Regulation and Pathology, MIFAB, Faculty of Biological Sciences, P. Universidad Católica de Chile, Alameda 340, Santiago, Chile.
Dev Biol. 2009 May 15;329(2):338-49. doi: 10.1016/j.ydbio.2009.03.007. Epub 2009 Mar 18.
Extracellular regulation of growth factor signaling is a key event for embryonic patterning. Heparan sulfate proteoglycans (HSPG) are among the molecules that regulate this signaling during embryonic development. Here we study the function of syndecan1 (Syn1), a cell-surface HSPG expressed in the non-neural ectoderm during early development of Xenopus embryos. Overexpression of Xenopus Syn1 (xSyn1) mRNA is sufficient to reduce BMP signaling, induce chordin expression and rescue dorso-ventral patterning in ventralized embryos. Experiments using chordin morpholinos established that xSyn1 mRNA can inhibit BMP signaling in the absence of chordin. Knockdown of xSyn1 resulted in a reduction of BMP signaling and expansion of the neural plate with the concomitant reduction of the non-neural ectoderm. Overexpression of xSyn1 mRNA in xSyn1 morphant embryos resulted in a biphasic effect, with BMP being inhibited at high concentrations and activated at low concentrations of xSyn1. Interestingly, the function of xSyn1 on dorso-ventral patterning and BMP signaling is specific for this HSPG. In summary, we report that xSyn1 regulates dorso-ventral patterning of the ectoderm through modulation of BMP signaling.
生长因子信号的细胞外调节是胚胎模式形成的关键事件。硫酸乙酰肝素蛋白聚糖(HSPG)是在胚胎发育过程中调节这种信号的分子之一。在这里,我们研究了syndecan1(Syn1)的功能,它是一种细胞表面HSPG,在非洲爪蟾胚胎早期发育期间在非神经外胚层中表达。非洲爪蟾Syn1(xSyn1)mRNA的过表达足以降低BMP信号,诱导脊索蛋白表达并挽救腹侧化胚胎的背腹模式。使用脊索蛋白吗啉代的实验表明,xSyn1 mRNA在没有脊索蛋白的情况下可以抑制BMP信号。敲低xSyn1导致BMP信号减少和神经板扩展,同时非神经外胚层减少。在xSyn1 morphant胚胎中过表达xSyn1 mRNA产生双相效应,在高浓度的xSyn1下BMP被抑制,而在低浓度下被激活。有趣的是,xSyn1对背腹模式和BMP信号的功能对这种HSPG具有特异性。总之,我们报告xSyn1通过调节BMP信号来调节外胚层的背腹模式。