Localized JNK signaling regulates organ size during development

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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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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.
Xiaoyan Zheng

Department of Anatomy and Regenerative Biology, School of Medicine and Health Sciences, The George Washington University, Washington, United States

Competing interests
The authors declare that no competing interests exist.
José Carlos Pastor-Pareja

School of Life Sciences, Tsinghua University, Beijing, China

Competing interests
The authors declare that no competing interests exist.
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.
Philip A Beachy

Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, Stanford, United States

Competing interests
The authors declare that no competing interests exist.
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.

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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.