Wnt/PCP controls spreading of Wnt/β-catenin signals by cytonemes in vertebrates
- University of Exeter, United Kingdom
- Karlsruhe Institute of Technology, Germany
- Duke-NUS Medical School, Singapore
- University Hospital Heidelberg, Germany
- John von Neumann Institute for Computing, Germany
- University of Heidelberg, Germany
Abstract
Signaling filopodia, termed cytonemes, are dynamic actin-based membrane structures that regulate the exchange of signaling molecules and their receptors within tissues. However, how cytoneme formation is regulated remains unclear. Here, we show that Wnt/PCP autocrine signaling controls the emergence of cytonemes, and that cytonemes subsequently control paracrine Wnt/β-catenin signal activation. Upon binding of the Wnt family member Wnt8a, the receptor tyrosine kinase Ror2 gets activated. Ror2/PCP signaling leads to induction of cytonemes, which mediate transport of Wnt8a to neighboring cells. In the Wnt receiving cells, Wnt8a on cytonemes triggers Wnt/β-catenin-dependent gene transcription and proliferation. We show that cytoneme-based Wnt transport operates in diverse processes, including zebrafish development, the murine intestinal crypt, and human cancer organoids, demonstrating that Wnt transport by cytonemes and its control via the Ror2 pathway is highly conserved in vertebrates.
Data availability
All of the data supporting this paper is available via the Dryad repository (https://dx.doi.org/10.5061/dryad.38q5pc1)
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Data from: Wnt/PCP controls spreading of Wnt/β-catenin signals by cytonemes in vertebratesAvailable at Dryad Digital Repository under a CC0 Public Domain Dedication.
Article and author information
Author details
Johannes Stegmaier
Gerd Ulrich Nienhaus
Funding
Living Systems Institute (Start-up)
- Steffen Scholpp
Boehringer Ingelheim Fonds (Exploration)
- Steffen Scholpp
Deutsche Forschungsgemeinschaft (Scho847-5)
- Steffen Scholpp
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Thomas B Kornberg, University of California, San Francisco, United States
Version history
- Received: March 24, 2018
- Accepted: July 16, 2018
- Accepted Manuscript published: July 31, 2018 (version 1)
- Version of Record published: August 10, 2018 (version 2)
Copyright
© 2018, Mattes 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.
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Wnt/PCP controls spreading of Wnt/β-catenin signals by cytonemes in vertebrates
eLife 7:e36953.
https://doi.org/10.7554/eLife.36953
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