ZFIN ID: ZDB-PUB-180801-1
Wnt/PCP controls spreading of Wnt/β-catenin signals by cytonemes in vertebrates
Mattes, B., Dang, Y., Greicius, G., Kaufmann, L.T., Prunsche, B., Rosenbauer, J., Stegmaier, J., Mikut, R., Özbek, S., Nienhaus, G.U., Schug, A., Virshup, D.M., Scholpp, S.
Date: 2018
Source: eLIFE 7: (Journal)
Registered Authors: Mattes, Banjamin, Mikut, Ralf, Scholpp, Steffen
Keywords: developmental biology, zebrafish
MeSH Terms:
  • Animals
  • Autocrine Communication/genetics
  • Cell Polarity/genetics
  • Cytoskeletal Proteins/genetics*
  • Gene Expression Regulation, Developmental/genetics
  • Humans
  • Mice
  • Paracrine Communication/genetics
  • Pseudopodia/genetics
  • Pseudopodia/metabolism
  • Receptor Tyrosine Kinase-like Orphan Receptors/genetics*
  • Wnt Proteins/genetics*
  • Wnt Signaling Pathway/genetics
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • Zebrafish Proteins/genetics*
  • beta Catenin/genetics*
PubMed: 30060804 Full text @ Elife
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.