title: Localized JNK signaling regulates organ size during development.
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.
authors.affiliation: Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States.
authors.forename: Helen Rankin
authors.initials: HR
authors.lastname: Willsey
authors.affiliation: 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.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States.
authors.forename: José
authors.identifier: 0000-0002-3823-4473
authors.initials: J
authors.lastname: Carlos Pastor-Pareja
authors.affiliation: Department of Psychiatry, University of California, San Francisco, San Francisco, United States.
authors.forename: A Jeremy
authors.initials: AJ
authors.lastname: Willsey
authors.affiliation: 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.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Beachy
authors.affiliation: 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.
authors.forename: Tian
authors.identifier: 0000-0002-2160-0027
authors.initials: T
authors.lastname: Xu
mesh_terms: D000818:Animals; D057506:Arthropod Antennae / Q000196:embryology / Q000254:growth & development; D004330:Drosophila / Q000196:embryology* / Q000378:metabolism; D005121:Extremities / Q000196:embryology / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental; D020935:MAP Kinase Signaling System; D038081:Organogenesis; D014921:Wings, Animal / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism
keywords: D. melanogaster; Hedgehog; Hippo; JNK; TRAF4; development; developmental biology; size control; stem cells