Wnt/PCP Controls Spreading of Wnt/β-catenin Signals by Cytonemes in Vertebrates

Overview

Journal Elife

Specialty Biology

Date 2018 Aug 1

PMID 30060804

Citations 64

Authors

Benjamin Mattes

Yonglong Dang

Gediminas Greicius

Lilian Tamara Kaufmann

Benedikt Prunsche

Jakob Rosenbauer

Johannes Stegmaier

Ralf Mikut

Suat Ozbek

Gerd Ulrich Nienhaus

Alexander Schug

David M Virshup

Steffen Scholpp

Affiliations

Soon will be listed here.

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/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.

Citing Articles

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