Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1782429298350620672 |
---|---|
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 |
format | Online Article Text |
id | pubmed-4848088 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT willseyhelenrankin localizedjnksignalingregulatesorgansizeduringdevelopment AT zhengxiaoyan localizedjnksignalingregulatesorgansizeduringdevelopment AT carlospastorparejajose localizedjnksignalingregulatesorgansizeduringdevelopment AT willseyajeremy localizedjnksignalingregulatesorgansizeduringdevelopment AT beachyphilipa localizedjnksignalingregulatesorgansizeduringdevelopment AT xutian localizedjnksignalingregulatesorgansizeduringdevelopment |