Direct visualization of a native Wnt in vivo reveals that a long-range Wnt gradient forms by extracellular dispersal

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Abstract

Wnts are evolutionarily conserved signaling proteins with essential roles in development and disease that have often been thought to spread between cells and signal at a distance. However, recent studies have challenged this model, and whether long-distance extracellular Wnt dispersal occurs and is biologically relevant is debated. Understanding fundamental aspects of Wnt dispersal has been limited by challenges with observing endogenous ligands in vivo, which has prevented directly testing hypotheses. Here, we have generated functional, fluorescently tagged alleles for a C. elegans Wnt homolog and for the first time visualized a native, long-range Wnt gradient in a living animal. Live imaging of Wnt along with source and responding cell membranes provided support for free, extracellular dispersal. By limiting Wnt transfer between cells, we confirmed that extracellular spreading shapes a long-range gradient and is critical for neuroblast migration. These results provide direct evidence that Wnts spread extracellularly to regulate aspects of long-range signaling.

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All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 1 and 6.

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Ariel M Pani

Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, United States

For correspondence
ariel.pani@gmail.com

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-9338-9750
Bob Goldstein

Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, United States

Competing interests
The authors declare that no competing interests exist.

Funding

National Institute of General Medical Sciences (R01 GM083071)

Bob Goldstein

National Institute of General Medical Sciences (F32 GM115151)

Ariel M Pani

American Cancer Society (PF-16-030 DDC)

Ariel M Pani

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.