Collagen triple helix repeat containing 1a (Cthrc1a) regulates cell adhesion and migration during gastrulation in zebrafish
Collagen triple helix repeat containing 1a (Cthrc1a) regulates cell adhesion and migration during gastrulation in zebrafish
复制标题
含有 1a (Cthrc1a) 的胶原三螺旋重复序列调节斑马鱼原肠胚形成过程中的细胞粘附和迁移
DOI：
10.1016/j.yexcr.2019.04.033
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发表时间：
2019-08-01
影响因子：
3.7
通讯作者：
Shi, De-Li
中科院分区：
文献类型：
--
作者：
Cheng, Xiao-Ning;Shao, Ming;Shi, De-Li
细胞粘附和迁移是早期胚胎原肠胚形成和癌症转移过程中的关键细胞行为。 Cthrc1 是一种在脊椎动物中高度保守的分泌蛋白；它在受伤和患病的动脉以及恶性癌症中表达上调。越来越多的证据表明其表达和活性与癌症进展和炎症性疾病有关。然而，它调节细胞迁移的机制及其在早期发育过程中的意义仍不清楚。在这里，我们表明斑马鱼 Cthrc1a 在下胚层细胞中表达，并且是原肠胚形成过程中细胞粘附和迁移所必需的。整个胚胎中ahrc1a的敲低抑制了外延和会聚伸展运动，并减少了前后轴的伸长。细胞粘附测定表明，Cthrc1a 对于中内胚层细胞与纤连蛋白包被的基质相互作用以及延长极化细胞突起是必需的。此外，分泌的 Cthrc1a 蛋白在胚盘细胞之间有效扩散，并以整合素依赖性方式被邻近细胞招募。一致地，Cthrc1a 和整合素β1 在前后轴伸长中存在功能相互作用。这些结果提供了对 Cthrc1a 在胚胎轴伸长过程中细胞粘附和迁移调节中的功能的深入了解。
Cell adhesion and migration are key cell behaviours during gastrulation in early embryos and metastasis in cancers. Cthrc1 is a secreted protein highly conserved among vertebrates; it is upregulated in injured and diseased arteries, as well as in malignant cancers. There is increasing evidence showing that its expression and activity are associated with cancer progression and inflammatory diseases. However, the mechanism by which it regulates cell migration, and its implication during early development remains unclear. Here we show that zebrafish Cthrc1a is expressed in hypoblast cells, and is required for cell adhesion and migration during gastrulation. Knockdown of ahrc1a in whole embryo inhibits epiboly and convergent extension movements, and reduces the elongation of anteroposterior axis. Cell adhesion assay indicates that Cthrc1a is necessary for mesendoderm cells to interact with fibronectin-coated substratum, and to extend polarised cellular protrusions. Moreover, secreted Cthrc1a proteins diffuse efficiently between blastoderm cells and are recruited by neighbouring cells in an integrin-dependent manner. Consistently, there exists a functional interaction between Cthrc1a and integrin beta 1 in anteroposterior axis elongation. These results provide insight into the function of Cthrc1a in the regulation of cell adhesion and migration during embryonic axis elongation.