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Vangl2 promotes the formation of long cytonemes to enable distant Wnt/β-catenin signaling.

Publication ,  Journal Article
Brunt, L; Greicius, G; Rogers, S; Evans, BD; Virshup, DM; Wedgwood, KCA; Scholpp, S
Published in: Nat Commun
April 6, 2021

Wnt signaling regulates cell proliferation and cell differentiation as well as migration and polarity during development. However, it is still unclear how the Wnt ligand distribution is precisely controlled to fulfil these functions. Here, we show that the planar cell polarity protein Vangl2 regulates the distribution of Wnt by cytonemes. In zebrafish epiblast cells, mouse intestinal telocytes and human gastric cancer cells, Vangl2 activation generates extremely long cytonemes, which branch and deliver Wnt protein to multiple cells. The Vangl2-activated cytonemes increase Wnt/β-catenin signaling in the surrounding cells. Concordantly, Vangl2 inhibition causes fewer and shorter cytonemes to be formed and reduces paracrine Wnt/β-catenin signaling. A mathematical model simulating these Vangl2 functions on cytonemes in zebrafish gastrulation predicts a shift of the signaling gradient, altered tissue patterning, and a loss of tissue domain sharpness. We confirmed these predictions during anteroposterior patterning in the zebrafish neural plate. In summary, we demonstrate that Vangl2 is fundamental to paracrine Wnt/β-catenin signaling by controlling cytoneme behaviour.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

April 6, 2021

Volume

12

Issue

1

Start / End Page

2058

Location

England

Related Subject Headings

  • Zebrafish
  • Wnt Signaling Pathway
  • Telocytes
  • Systems Analysis
  • Pseudopodia
  • Paracrine Communication
  • Neurogenesis
  • Neural Plate
  • Mice, Inbred C57BL
  • Mice
 

Citation

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MLA
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Brunt, L., Greicius, G., Rogers, S., Evans, B. D., Virshup, D. M., Wedgwood, K. C. A., & Scholpp, S. (2021). Vangl2 promotes the formation of long cytonemes to enable distant Wnt/β-catenin signaling. Nat Commun, 12(1), 2058. https://doi.org/10.1038/s41467-021-22393-9
Brunt, Lucy, Gediminas Greicius, Sally Rogers, Benjamin D. Evans, David M. Virshup, Kyle C. A. Wedgwood, and Steffen Scholpp. “Vangl2 promotes the formation of long cytonemes to enable distant Wnt/β-catenin signaling.Nat Commun 12, no. 1 (April 6, 2021): 2058. https://doi.org/10.1038/s41467-021-22393-9.
Brunt L, Greicius G, Rogers S, Evans BD, Virshup DM, Wedgwood KCA, et al. Vangl2 promotes the formation of long cytonemes to enable distant Wnt/β-catenin signaling. Nat Commun. 2021 Apr 6;12(1):2058.
Brunt, Lucy, et al. “Vangl2 promotes the formation of long cytonemes to enable distant Wnt/β-catenin signaling.Nat Commun, vol. 12, no. 1, Apr. 2021, p. 2058. Pubmed, doi:10.1038/s41467-021-22393-9.
Brunt L, Greicius G, Rogers S, Evans BD, Virshup DM, Wedgwood KCA, Scholpp S. Vangl2 promotes the formation of long cytonemes to enable distant Wnt/β-catenin signaling. Nat Commun. 2021 Apr 6;12(1):2058.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

April 6, 2021

Volume

12

Issue

1

Start / End Page

2058

Location

England

Related Subject Headings

  • Zebrafish
  • Wnt Signaling Pathway
  • Telocytes
  • Systems Analysis
  • Pseudopodia
  • Paracrine Communication
  • Neurogenesis
  • Neural Plate
  • Mice, Inbred C57BL
  • Mice