Hemicentin 2 and Fibulin 1 are required for epidermal-dermal junction formation and fin mesenchymal cell migration during zebrafish development.
Hemicentin 2 and Fibulin 1 are required for epidermal-dermal junction formation and fin mesenchymal cell migration during zebrafish development.
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DOI：
10.1016/j.ydbio.2012.06.023
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发表时间：
2012-09-15
影响因子：
2.7
通讯作者：
Hammerschmidt, Matthias
中科院分区：
文献类型：
--
作者：
Feitosa, Natalia Martins;Zhang, Jinli;Carney, Thomas J.;Metzger, Manuel;Korzh, Vladimir;Bloch, Wilhelm;Hammerschmidt, Matthias
关键词：
半纤维蛋白1（Hmcn 1）和半纤维蛋白2（Hmcn 2）属于细胞外基质（ECM）蛋白的纤蛋白家族，其在多种脊椎动物组织的发育和稳态中起关键作用。最近，我们已经证明，斑马鱼Hmcn 1（也称为Fibulin 6）的突变会导致大量的鳍起泡，类似于弗雷泽综合征基因Fras 1引起的缺陷。与此相反，Hmcn 2在脊椎动物发育过程中的作用迄今尚未得到表征。在斑马鱼中，hmcn 2和fibulin家族的另一个成员fibulin 1（fbln 1）一样，主要在鳍间充质细胞和发育中的体节中表达，与hmcn 1的严格上皮表达形成对比。虽然反义吗啉代寡核苷酸（MO）为基础的敲低hmcn 2没有产生任何明显的缺陷，hmcn 2/fbln 1双敲低鱼显示在躯干起泡，指出这些蛋白质的重要贡献，从中胚层来源适当的表皮-真皮交界处的形成。相反，与hmcn 1突变体不同，hmcn 2/fbln 1双敲除鱼的鳍褶皱中的表皮-真皮连接处仅受到中度影响。相反，它们显示鳍间充质细胞迁移到鳍褶中受损，这表明Hmcn 2和Fbln 1在重塑鳍褶表皮间空间的ECM中起着至关重要的作用，这是成纤维细胞向内生长的先决条件。TEM分析表明，这种ECM重塑发生在放线菌的水平，间充质细胞的胶原迁移基板，并在水平的交叉纤维，这类似于哺乳动物的微纤维。这项工作提供了第一次深入了解Hmcn 2在脊椎动物发育过程中的作用，确定它作为一个进化保守的蛋白质，与Fbln 1C和/或Fbln 1D亚型的功能冗余，以调节组织粘附和细胞迁移，同时扩展目前的知识脊椎动物Fbln 1的功能。
Hemicentin 1 (Hmcn1) and Hemicentin 2 (Hmcn2) belong to the fibulin family of extracellular matrix (ECM) proteins that play pivotal roles during development and homeostasis of a variety of vertebrate tissues. Recently, we have shown that mutations in zebrafish Hmcn1, also called Fibulin 6, lead to massive fin blistering, similar to the defects caused by the Fraser syndrome gene Fras1. In contrast, the role of Hmcn2 during vertebrate development has thus far been uncharacterized. In zebrafish, hmcn2, like fibulin 1 (fbln1), another member of the fibulin family, is predominantly expressed in fin mesenchymal cells and developing somites, contrasting the strict epithelial expression of hmcn1. While antisense morpholino oligonucleotide (MO) – based knockdown of hmcn2 did not yield any discernable defects, hmcn2/fbln1 double knockdown fish displayed blistering in the trunk, pointing to an essential contribution of these proteins from mesodermal sources for proper epidermal-dermal junction formation. In contrast, and unlike hmcn1 mutants, epidermal-dermal junctions in the fin folds of hmcn2/fbln1 double knockdown fish were only moderately affected. Instead, they displayed impaired migration of fin mesenchymal cells into the fin folds, pointing to a crucial role of Hmcn2 and Fbln1 to remodel the ECM of the fin fold interepidermal space, which is a prerequisite for fibroblast ingrowth. TEM analyses suggest that this ECM remodeling occurs at the level of actinotrichia, the collageneous migration substrate of mesenchymal cells, and at the level of cross fibers, which resemble mammalian microfibers. This work provides first insights into the role of Hmcn2 during vertebrate development, identifying it as an evolutionary conserved protein that acts in functional redundancy with Fbln1C and/or Fbln1D isoforms to regulate tissue adhesion and cell migration, while extending current knowledge of the functions of vertebrate Fbln1.
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纤维蛋白-2在斑马鱼脊索和血管形态发生中的重要作用。
影响因子：
2.5
作者：
Gansner, John M.;Madsen, Erik C.;Mecham, Robert P.;Gitlin, Jonathan D.
通讯作者：
Gitlin, Jonathan D.
影响因子：
2.7
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1038/89683
发表时间：
2001-07-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
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通讯作者：
Hohenester, E
影响因子：
64.5
作者：
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通讯作者：
RUOSLAHTI, E