Localized JNK signaling regulates organ size during development
Helen Rankin Willsey,
Xiaoyan Zheng,
José Carlos Pastor-Pareja,
A Jeremy Willsey,
Philip A Beachy,
Tian Xu
Affiliations
Helen Rankin Willsey
Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States
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
Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States
A Jeremy Willsey
Department of Psychiatry, University of California, San Francisco, San Francisco, United States
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
Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States; State Key Laboratory of Genetic Engineering and National Center for International Research, Fudan-Yale Biomedical Research Center, Institute of Developmental Biology and Molecular Medicine, School of Life Sciences, Fudan University, Shanghai, China
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.
