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利用高反应性 Wnt/β-连环蛋白信号报告转基因斑马鱼可视化和探索 Tcf/Lef 功能。

Visualization and exploration of Tcf/Lef function using a highly responsive Wnt/β-catenin signaling-reporter transgenic zebrafish.

机构信息

Division of Cell Regulation Systems, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

出版信息

Dev Biol. 2012 Oct 1;370(1):71-85. doi: 10.1016/j.ydbio.2012.07.016. Epub 2012 Jul 25.

DOI:10.1016/j.ydbio.2012.07.016
PMID:22842099
Abstract

Evolutionarily conserved Tcf/Lef transcription factors (Lef1, Tcf7, Tcf7l1, and Tcf7l2) mediate gene expression regulated by Wnt/β-catenin signaling, which has multiple roles in early embryogenesis, organogenesis, adult tissue homeostasis, and tissue regeneration. However, the spatiotemporal dynamics of Tcf/Lef activity during these events remain poorly understood. We generated stable transgenic zebrafish lines carrying a new Wnt/β-catenin signaling reporter, Tcf/Lef-miniP:dGFP. The reporter revealed the transcriptional activities of four Tcf/Lef members controlled by Wnt/β-catenin signaling, which were expressed in known Wnt/β-catenin signaling-active sites during embryogenesis, organ development and growth, and tissue regeneration. We used the transgenic lines to demonstrate the contribution of Tcf/Lef-mediated Wnt/β-catenin signaling to the development of the anterior lateral line, dorsal and secondary posterior lateral lines, and gill filaments. Thus, these reporter lines are highly useful tools for studying Tcf/Lef-mediated Wnt/β-catenin signaling-dependent processes.

摘要

进化上保守的 Tcf/Lef 转录因子(Lef1、Tcf7、Tcf7l1 和 Tcf7l2)介导 Wnt/β-连环蛋白信号转导调节的基因表达,该信号在胚胎早期发育、器官发生、成人组织稳态和组织再生中具有多种作用。然而,这些事件中 Tcf/Lef 活性的时空动态仍知之甚少。我们生成了稳定的转基因斑马鱼系,携带新的 Wnt/β-连环蛋白信号报告基因 Tcf/Lef-miniP:dGFP。该报告基因揭示了受 Wnt/β-连环蛋白信号控制的四个 Tcf/Lef 成员的转录活性,这些成员在胚胎发生、器官发育和生长以及组织再生过程中表达于已知的 Wnt/β-连环蛋白信号活性部位。我们使用这些转基因系证明了 Tcf/Lef 介导的 Wnt/β-连环蛋白信号对前侧线、背侧和次级后侧线以及鳃丝发育的贡献。因此,这些报告基因系是研究 Tcf/Lef 介导的 Wnt/β-连环蛋白信号依赖性过程的非常有用的工具。

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