Cargando…

YAP is essential for mechanical force production and epithelial cell proliferation during lung branching morphogenesis

Branching morphogenesis is a fundamental program for tissue patterning. We show that active YAP, a key mediator of Hippo signaling, is distributed throughout the murine lung epithelium and loss of epithelial YAP severely disrupts branching. Failure to branch is restricted to regions where YAP activi...

Descripción completa

Detalles Bibliográficos
Autores principales: Lin, Chuwen, Yao, Erica, Zhang, Kuan, Jiang, Xuan, Croll, Stacey, Thompson-Peer, Katherine, Chuang, Pao-Tien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360446/
https://www.ncbi.nlm.nih.gov/pubmed/28323616
http://dx.doi.org/10.7554/eLife.21130
_version_ 1782516607487049728
author Lin, Chuwen
Yao, Erica
Zhang, Kuan
Jiang, Xuan
Croll, Stacey
Thompson-Peer, Katherine
Chuang, Pao-Tien
author_facet Lin, Chuwen
Yao, Erica
Zhang, Kuan
Jiang, Xuan
Croll, Stacey
Thompson-Peer, Katherine
Chuang, Pao-Tien
author_sort Lin, Chuwen
collection PubMed
description Branching morphogenesis is a fundamental program for tissue patterning. We show that active YAP, a key mediator of Hippo signaling, is distributed throughout the murine lung epithelium and loss of epithelial YAP severely disrupts branching. Failure to branch is restricted to regions where YAP activity is removed. This suggests that YAP controls local epithelial cell properties. In support of this model, mechanical force production is compromised and cell proliferation is reduced in Yap mutant lungs. We propose that defective force generation and insufficient epithelial cell number underlie the branching defects. Through genomic analysis, we also uncovered a feedback control of pMLC levels, which is critical for mechanical force production, likely through the direct induction of multiple regulators by YAP. Our work provides a molecular pathway that could control epithelial cell properties required for proper morphogenetic movement and pattern formation. DOI: http://dx.doi.org/10.7554/eLife.21130.001
format Online
Article
Text
id pubmed-5360446
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher eLife Sciences Publications, Ltd
record_format MEDLINE/PubMed
spelling pubmed-53604462017-03-22 YAP is essential for mechanical force production and epithelial cell proliferation during lung branching morphogenesis Lin, Chuwen Yao, Erica Zhang, Kuan Jiang, Xuan Croll, Stacey Thompson-Peer, Katherine Chuang, Pao-Tien eLife Developmental Biology and Stem Cells Branching morphogenesis is a fundamental program for tissue patterning. We show that active YAP, a key mediator of Hippo signaling, is distributed throughout the murine lung epithelium and loss of epithelial YAP severely disrupts branching. Failure to branch is restricted to regions where YAP activity is removed. This suggests that YAP controls local epithelial cell properties. In support of this model, mechanical force production is compromised and cell proliferation is reduced in Yap mutant lungs. We propose that defective force generation and insufficient epithelial cell number underlie the branching defects. Through genomic analysis, we also uncovered a feedback control of pMLC levels, which is critical for mechanical force production, likely through the direct induction of multiple regulators by YAP. Our work provides a molecular pathway that could control epithelial cell properties required for proper morphogenetic movement and pattern formation. DOI: http://dx.doi.org/10.7554/eLife.21130.001 eLife Sciences Publications, Ltd 2017-03-21 /pmc/articles/PMC5360446/ /pubmed/28323616 http://dx.doi.org/10.7554/eLife.21130 Text en © 2017, Lin 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
Lin, Chuwen
Yao, Erica
Zhang, Kuan
Jiang, Xuan
Croll, Stacey
Thompson-Peer, Katherine
Chuang, Pao-Tien
YAP is essential for mechanical force production and epithelial cell proliferation during lung branching morphogenesis
title YAP is essential for mechanical force production and epithelial cell proliferation during lung branching morphogenesis
title_full YAP is essential for mechanical force production and epithelial cell proliferation during lung branching morphogenesis
title_fullStr YAP is essential for mechanical force production and epithelial cell proliferation during lung branching morphogenesis
title_full_unstemmed YAP is essential for mechanical force production and epithelial cell proliferation during lung branching morphogenesis
title_short YAP is essential for mechanical force production and epithelial cell proliferation during lung branching morphogenesis
title_sort yap is essential for mechanical force production and epithelial cell proliferation during lung branching morphogenesis
topic Developmental Biology and Stem Cells
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360446/
https://www.ncbi.nlm.nih.gov/pubmed/28323616
http://dx.doi.org/10.7554/eLife.21130
work_keys_str_mv AT linchuwen yapisessentialformechanicalforceproductionandepithelialcellproliferationduringlungbranchingmorphogenesis
AT yaoerica yapisessentialformechanicalforceproductionandepithelialcellproliferationduringlungbranchingmorphogenesis
AT zhangkuan yapisessentialformechanicalforceproductionandepithelialcellproliferationduringlungbranchingmorphogenesis
AT jiangxuan yapisessentialformechanicalforceproductionandepithelialcellproliferationduringlungbranchingmorphogenesis
AT crollstacey yapisessentialformechanicalforceproductionandepithelialcellproliferationduringlungbranchingmorphogenesis
AT thompsonpeerkatherine yapisessentialformechanicalforceproductionandepithelialcellproliferationduringlungbranchingmorphogenesis
AT chuangpaotien yapisessentialformechanicalforceproductionandepithelialcellproliferationduringlungbranchingmorphogenesis