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光激活卷曲蛋白 7 揭示了非经典 Wnt 信号在中胚层细胞迁移中的允许作用。

Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration.

机构信息

Institute of Science and Technology Austria, Klosterneuburg, Austria.

Centre for Mechanochemical Cell Biology and Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, United Kingdom.

出版信息

Elife. 2019 Jan 16;8:e42093. doi: 10.7554/eLife.42093.

DOI:10.7554/eLife.42093
PMID:30648973
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6365057/
Abstract

Non-canonical Wnt signaling plays a central role for coordinated cell polarization and directed migration in metazoan development. While spatiotemporally restricted activation of non-canonical Wnt-signaling drives cell polarization in epithelial tissues, it remains unclear whether such instructive activity is also critical for directed mesenchymal cell migration. Here, we developed a light-activated version of the non-canonical Wnt receptor Frizzled 7 (Fz7) to analyze how restricted activation of non-canonical Wnt signaling affects directed anterior axial mesendoderm (prechordal plate, ppl) cell migration within the zebrafish gastrula. We found that Fz7 signaling is required for ppl cell protrusion formation and migration and that spatiotemporally restricted ectopic activation is capable of redirecting their migration. Finally, we show that uniform activation of Fz7 signaling in ppl cells fully rescues defective directed cell migration in mutant embryos. Together, our findings reveal that in contrast to the situation in epithelial cells, non-canonical Wnt signaling functions permissively rather than instructively in directed mesenchymal cell migration during gastrulation.

摘要

非经典 Wnt 信号通路在多细胞生物的胚胎发育过程中协调细胞极化和定向迁移方面发挥着核心作用。虽然非经典 Wnt 信号通路的时空限制激活可驱动上皮组织中的细胞极化，但对于定向的间质细胞迁移，这种指令性活性是否也很关键仍不清楚。在这里，我们开发了一种光激活的非经典 Wnt 受体卷曲蛋白 7（Fz7）的变体，以分析非经典 Wnt 信号的受限激活如何影响斑马鱼胚胎中轴前中胚层（前脑板，ppl）细胞的定向迁移。我们发现 Fz7 信号对于 ppl 细胞突起的形成和迁移是必需的，并且时空限制的异位激活能够改变它们的迁移方向。最后，我们表明在 ppl 细胞中均匀激活 Fz7 信号可以完全挽救 突变体胚胎中定向细胞迁移的缺陷。总之，我们的研究结果表明，与上皮细胞的情况相反，在原肠胚形成过程中，非经典 Wnt 信号在定向的间质细胞迁移中起允许而非指令性作用。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22c8/6365057/3db8c9d546e5/elife-42093-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22c8/6365057/c1219e01df88/elife-42093-fig1-figsupp1.jpg
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