Localized JNK signaling regulates organ size during development

  1. Helen Rankin Willsey
  2. Xiaoyan Zheng
  3. José Carlos Pastor-Pareja
  4. A Jeremy Willsey
  5. Philip A Beachy
  6. Tian Xu  Is a corresponding author
  1. Howard Hughes Medical Institute, Yale University School of Medicine, United States
  2. Howard Hughes Medical Institute, Stanford University School of Medicine, United States
  3. University of California, San Francisco, United States

Abstract

A fundamental question of biology is what determines organ size. Despite demonstrations that factors within organs determine their sizes, intrinsic size control mechanisms remain elusive. Here we show that Drosophila wing size is regulated by JNK signaling during development. JNK is active in a stripe along the center of developing wings, and modulating JNK signaling within this stripe changes organ size. This JNK stripe influences proliferation in a non-canonical, Jun-independent manner by inhibiting the Hippo pathway. Localized JNK activity is established by Hedgehog signaling, where Ci elevates dTRAF1 expression. As the dTRAF1 homolog, TRAF4, is amplified in numerous cancers, these findings provide a new mechanism for how the Hedgehog pathway could contribute to tumorigenesis, and, more importantly, provides a new strategy for cancer therapies. Finally, modulation of JNK signaling centers in developing antennae and legs changes their sizes, suggesting a more generalizable role for JNK signaling in developmental organ size control.

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Author details

  1. Helen Rankin Willsey

    Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Xiaoyan Zheng

    Departments of Biochemistry and Developmental Biology, Institute for Stem Cell Biology and Regenerative Medicine, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. José Carlos Pastor-Pareja

    Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. A Jeremy Willsey

    Department of Psychiatry, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Philip A Beachy

    Departments of Biochemistry and Developmental Biology, Institute for Stem Cell Biology and Regenerative Medicine, Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Tian Xu

    Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States
    For correspondence
    tian.xu@yale.edu
    Competing interests
    The authors declare that no competing interests exist.

Copyright

© 2016, Willsey et al.

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.

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  1. Helen Rankin Willsey
  2. Xiaoyan Zheng
  3. José Carlos Pastor-Pareja
  4. A Jeremy Willsey
  5. Philip A Beachy
  6. Tian Xu
(2016)
Localized JNK signaling regulates organ size during development
eLife 5:e11491.
https://doi.org/10.7554/eLife.11491

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https://doi.org/10.7554/eLife.11491