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Localized JNK signaling regulates organ size during development

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 stri...

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Detalles Bibliográficos
Autores principales: Willsey, Helen Rankin, Zheng, Xiaoyan, Carlos Pastor-Pareja, José, Willsey, A Jeremy, Beachy, Philip A, Xu, Tian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848088/
https://www.ncbi.nlm.nih.gov/pubmed/26974344
http://dx.doi.org/10.7554/eLife.11491
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author Willsey, Helen Rankin
Zheng, Xiaoyan
Carlos Pastor-Pareja, José
Willsey, A Jeremy
Beachy, Philip A
Xu, Tian
author_facet Willsey, Helen Rankin
Zheng, Xiaoyan
Carlos Pastor-Pareja, José
Willsey, A Jeremy
Beachy, Philip A
Xu, Tian
author_sort Willsey, Helen Rankin
collection PubMed
description 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. DOI: http://dx.doi.org/10.7554/eLife.11491.001
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spelling pubmed-48480882016-04-29 Localized JNK signaling regulates organ size during development Willsey, Helen Rankin Zheng, Xiaoyan Carlos Pastor-Pareja, José Willsey, A Jeremy Beachy, Philip A Xu, Tian eLife Developmental Biology and Stem Cells 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. DOI: http://dx.doi.org/10.7554/eLife.11491.001 eLife Sciences Publications, Ltd 2016-03-14 /pmc/articles/PMC4848088/ /pubmed/26974344 http://dx.doi.org/10.7554/eLife.11491 Text en © 2016, Willsey et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Developmental Biology and Stem Cells
Willsey, Helen Rankin
Zheng, Xiaoyan
Carlos Pastor-Pareja, José
Willsey, A Jeremy
Beachy, Philip A
Xu, Tian
Localized JNK signaling regulates organ size during development
title Localized JNK signaling regulates organ size during development
title_full Localized JNK signaling regulates organ size during development
title_fullStr Localized JNK signaling regulates organ size during development
title_full_unstemmed Localized JNK signaling regulates organ size during development
title_short Localized JNK signaling regulates organ size during development
title_sort localized jnk signaling regulates organ size during development
topic Developmental Biology and Stem Cells
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848088/
https://www.ncbi.nlm.nih.gov/pubmed/26974344
http://dx.doi.org/10.7554/eLife.11491
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AT willseyajeremy localizedjnksignalingregulatesorgansizeduringdevelopment
AT beachyphilipa localizedjnksignalingregulatesorgansizeduringdevelopment
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