Rapid differential transport of Nodal and Lefty on sulfated proteoglycan-rich extracellular matrix regulates left-right asymmetry in Xenopus
Rapid differential transport of Nodal and Lefty on sulfated proteoglycan-rich extracellular matrix regulates left-right asymmetry in Xenopus
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DOI：
10.1242/dev.056010
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发表时间：
2011-02-01
期刊：
影响因子：
4.6
通讯作者：
Wright, Christopher
中科院分区：
文献类型：
--
作者：
Marjoram, Lindsay;Wright, Christopher
胚胎组织内指导性配体及其反馈拮抗剂的时空动态分布，包括固有的稳定性和清除率，受到与细胞表面或细胞外基质（ECM）相互作用的影响。Nodal（这里是非洲爪蟾的Xnr1或Nodal1）和Lefty在中内胚层诱导中以交叉调节关系相互作用，并且是早期体节发生阶段胚胎中左右（LR）不对称的保守指导者。通过表达体内产生成熟功能性表位标记配体的Xnr1和Lefty前蛋白，我们发现ECM是Nodal和Lefty积累的主要表面。我们检测到Lefty比Nodal移动得更快，有证据表明ECM中完整的硫酸化蛋白聚糖促进了Nodal的显着长距离运动。我们建议，Nodal自动调节基本上是由快速配体转运辅助的，这是左侧LPM（侧板中胚层）中Nodal表达向前移位的基础，并推测更成熟的前部区域中更高水平的硫酸软骨素蛋白聚糖（CSPG）提供定向转运线索。免疫检测和生物化学分析表明，从左LPM到右LPM的左转移，提供了直接的证据，左侧衍生的左是一个显着的影响，以确保继续抑制右侧的Nodal表达，维持单侧表达的这种保守的决定因素的不对称性。
The spatiotemporally dynamic distribution of instructive ligands within embryonic tissue, and their feedback antagonists, including inherent stabilities and rates of clearance, are affected by interactions with cell surfaces or extracellular matrix (ECM). Nodal (here, Xnr1 or Nodal1 in Xenopus) and Lefty interact in a cross-regulatory relationship in mesendoderm induction, and are the conserved instructors of left-right (LR) asymmetry in early somitogenesis stage embryos. By expressing Xnr1 and Lefty pro-proteins that produce mature functional epitope-tagged ligands in vivo, we found that ECM is a principal surface of Nodal and Lefty accumulation. We detected Lefty moving faster than Nodal, with evidence that intact sulfated proteoglycans in the ECM facilitate the remarkable long distance movement of Nodal. We propose that Nodal autoregulation substantially aided by rapid ligand transport underlies the anteriorward shift of Nodal expression in the left LPM (lateral plate mesoderm), and speculate that the higher levels of chondroitin-sulfate proteoglycan (CSPG) in more mature anterior regions provide directional transport cues. Immunodetection and biochemical analysis showed transfer of Lefty from left LPM to right LPM, providing direct evidence that left-side-derived Lefty is a significant influence in ensuring the continued suppression of right-sided expression of Nodal, maintaining unilateral expression of this conserved determinant of asymmetry.