Wnt/PCP controls spreading of Wnt/β-catenin signals by cytonemes in vertebrates

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/planar cell polarity (PCP) autocrine signaling...

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Hauptverfasser: Mattes, Benjamin (VerfasserIn) , Kaufmann, Lilian (VerfasserIn) , Özbek, Suat (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: Jul 31, 2018
In: eLife
Year: 2018, Jahrgang: 7
ISSN:2050-084X
DOI:10.7554/eLife.36953
Online-Zugang:Verlag, Volltext: https://doi.org/10.7554/eLife.36953
Volltext
Verfasserangaben:Benjamin Mattes, Yonglong Dang, Gediminas Greicius, Lilian Tamara Kaufmann, Benedikt Prunsche, Jakob Rosenbauer, Johannes Stegmaier, Ralf Mikut, Suat Özbek, Gerd Ulrich Nienhaus, Alexander Schug, David M Virshup, Steffen Scholpp

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520 |a 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/planar cell polarity (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 becomes activated. Ror2/PCP signaling leads to the induction of cytonemes, which mediate the 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, 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. 
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