Emilin3 is required for notochord sheath integrity and interacts with Scube2 to regulate notochord-derived Hedgehog signals
Emilin3 is required for notochord sheath integrity and interacts with Scube2 to regulate notochord-derived Hedgehog signals
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DOI：
10.1242/dev.094078
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发表时间：
2013-11-15
期刊：
影响因子：
4.6
通讯作者：
Bonaldo, Paolo
中科院分区：
文献类型：
--
作者：
Corallo, Diana;Schiavinato, Alvise;Bonaldo, Paolo
脊索是一个短暂的和必不可少的结构，提供机械和信号线索的发展脊椎动物胚胎。在硬骨鱼类中，脊索由一个大的空泡细胞核心和一个分泌脊索鞘的细胞外层组成。在这项工作中，我们已经确定了细胞外基质糖蛋白Emilin3作为一种新的必需成分的斑马鱼脊索鞘。Emilin3基因敲低胚胎的脊索鞘发育受损。脊索的图案化活性也受到Emilin3的影响，如通过Emilin3耗尽的胚胎中Hedgehog（Hh）信号传导的增加和脊索中过表达Emilin3的胚胎中Hh信号传导的减少所揭示的。体外和体内实验表明Emilin3通过与脊索鞘中的许可因子Scube2相互作用来调节Hh配体的可用性。总的来说，这项研究揭示了EMILIN蛋白的新作用，并加强了脊索的结构和功能是严格联系在一起的概念。
The notochord is a transient and essential structure that provides both mechanical and signaling cues to the developing vertebrate embryo. In teleosts, the notochord is composed of a core of large vacuolated cells and an outer layer of cells that secrete the notochord sheath. In this work, we have identified the extracellular matrix glycoprotein Emilin3 as a novel essential component of the zebrafish notochord sheath. The development of the notochord sheath is impaired in Emilin3 knockdown embryos. The patterning activity of the notochord is also affected by Emilin3, as revealed by the increase of Hedgehog (Hh) signaling in Emilin3-depleted embryos and the decreased Hh signaling in embryos overexpressing Emilin3 in the notochord. In vitro and in vivo experiments indicate that Emilin3 modulates the availability of Hh ligands by interacting with the permissive factor Scube2 in the notochord sheath. Overall, this study reveals a new role for an EMILIN protein and reinforces the concept that structure and function of the notochord are strictly linked.