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

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Mattes, B; Dang, Y; Greicius, G; Kaufmann, LT; Prunsche, B; Rosenbauer, J; Stegmaier, J; Mikut, R; Özbek, S; Nienhaus, GU; Schug, A; Virshup, DM; Scholpp, S

Published Date

  • July 31, 2018

Published In

Volume / Issue

  • 7 /

PubMed ID

  • 30060804

Pubmed Central ID

  • 30060804

Electronic International Standard Serial Number (EISSN)

  • 2050-084X

Digital Object Identifier (DOI)

  • 10.7554/eLife.36953

Language

  • eng

Conference Location

  • England