Light-activated Frizzled7 reveals a permissive role of non-canonical Wnt signaling in mesendoderm cell migration
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 fz7 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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1-5, and figure supplements S1, S2, and S4-10
Article and author information
Author details
Funding
European Research Council (742573)
- Carl-Philipp Heisenberg
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Experiments involving zebrafish reported in this study included the creation and maintenance of transgenic mutant lines of zebrafish. In my role as Ethics Officer at IST Austria, I herewith confirm that the use of animals for experimental purposes within the scope of this study does not require the approval of the Ethics Committee at IST Austria. In line with EU directive 2010/63/EU on the protection of animals used for scientific purposes, Austrian legislation requires that the use of animals for scientific purposes has to be approved by the respective unit at the Federal Ministry of Education, Science, and Research. This process includes an ethical evaluation of the planned experiments as part of the harm-benefit analysis. Beyond that no further approval by the Ethics Committee at IST Austria is required. The respective approval number that covers the experiments that were performed is 66.018/0010-WF/II/3b/2014.Yours sincerely,Dr. Verena SeibothEthics Officer
Copyright
© 2019, Čapek et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 3,877
- views
-
- 648
- downloads
-
- 38
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Cell Biology
Dynamic interactions between gut mucosal cells and the external environment are essential to maintain gut homeostasis. Enterochromaffin (EC) cells transduce both chemical and mechanical signals and produce 5-hydroxytryptamine to mediate disparate physiological responses. However, the molecular and cellular basis for functional diversity of ECs remains to be adequately defined. Here, we integrated single-cell transcriptomics with spatial image analysis to identify 14 EC clusters that are topographically organized along the gut. Subtypes predicted to be sensitive to the chemical environment and mechanical forces were identified that express distinct transcription factors and hormones. A Piezo2+ population in the distal colon was endowed with a distinctive neuronal signature. Using a combination of genetic, chemogenetic, and pharmacological approaches, we demonstrated Piezo2+ ECs are required for normal colon motility. Our study constructs a molecular map for ECs and offers a framework for deconvoluting EC cells with pleiotropic functions.
-
- Cell Biology
- Developmental Biology
A study in mice reveals key interactions between proteins involved in fibroblast growth factor signaling and how they contribute to distinct stages of eye lens development.