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首页> 外文期刊>Cell and Tissue Research >Isthmin1, a secreted signaling protein, acts downstream of diverse embryonic patterning centers in development
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Isthmin1, a secreted signaling protein, acts downstream of diverse embryonic patterning centers in development

机译：Isthmin1，一种分泌的信号蛋白，在发展中的不同胚胎图案中心的下游起作用

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Extracellular signals play essential roles during embryonic patterning by providing positional information in a concentration-dependent manner, and many such signals, like Wnt, fibroblast growth factor (FGF), Hedgehog (Hh), and retinoic acid, act by being secreted into the extracellular space, thereby triggering receptor-mediated responses in other cells. Isthmin1 (ism1) is a secreted protein whose gene expression pattern coincides with that of early dorsal determinants, nodal ligand genes like sqt and cyc, and with fgf8 during various phases of zebrafish development. Ism1 functions in early embryonic patterning and development are poorly understood; however, it has recently been shown to interact with nodal pathway genes to control organ asymmetry in chicken. Here, we show that misexpression of ism1 deletion constructs disrupts embryonic patterning in zebrafish and exhibits genetic interactions with both Fgf and nodal signaling. Unlike Fgf and nodal pathway mutants, CRISPR/Cas9-engineered ism1 mutants did not show obvious developmental defects. Further, in vivo single molecule fluorescence correlation spectroscopy (FCCS) showed that Ism1 diffuses freely in the extra-cellular space, with a diffusion coefficient similar to that of Fgf8a; however, our measurements do not support direct molecular interactions between Ism1 and either nodal ligands or Fgf8a in the developing zebrafish embryo. Together, data from gain- and loss-of-function experiments suggest that zebrafish Ism1 plays a complex role in regulating extracellular signals during early embryonic development.
机译：细胞外信号以浓度依赖的方式提供位置信息，在胚胎形成过程中发挥重要作用，许多此类信号，如Wnt、成纤维细胞生长因子（FGF）、刺猬（Hh）和维甲酸，通过分泌到细胞外空间而起作用，从而触发其他细胞中的受体介导反应。ism1是一种分泌蛋白，其基因表达模式与早期背侧决定簇、结状配体基因（如sqt和cyc）以及斑马鱼发育不同阶段的fgf8的基因表达模式一致。Ism1在早期胚胎模式形成和发育中的作用尚不清楚；然而，最近的研究表明，它可以与淋巴结途径基因相互作用，从而控制鸡的器官不对称性。在这里，我们发现ism1缺失结构的错误表达扰乱了斑马鱼的胚胎模式，并表现出与Fgf和淋巴结信号的遗传相互作用。与Fgf和淋巴结途径突变体不同，CRISPR/Cas9工程ism1突变体没有显示出明显的发育缺陷。此外，体内单分子荧光相关光谱（FCCS）显示Ism1在细胞外空间自由扩散，扩散系数与Fgf8a相似；然而，我们的测量结果不支持Ism1与发育中的斑马鱼胚胎中的节点配体或Fgf8a之间的直接分子相互作用。总之，功能获得和功能丧失实验的数据表明，斑马鱼Ism1在早期胚胎发育期间调节细胞外信号中起着复杂的作用。

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