Negative Transpulmonary Pressure Disrupts Airway Morphogenesis by Suppressing Fgf10

Mechanical forces are increasingly recognized as important determinants of cell and tissue phenotype and also appear to play a critical role in organ development. During the fetal stages of lung morphogenesis, the pressure of the fluid within the lumen of the airways is higher than that within the c...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Alice E. Stanton, Katharine Goodwin, Aswin Sundarakrishnan, Jacob M. Jaslove, Jason P. Gleghorn, Amira L. Pavlovich, Celeste M. Nelson
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	tissue morphodynamics lung liquid mechanical stress mechanotransduction pulmonary hypoplasia congenital diaphragmatic hernia (CDH) Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/3c30d800ab4e4f2ca162659a19cca9ae
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3c30d800ab4e4f2ca162659a19cca9ae
record_format	dspace
spelling	oai:doaj.org-article:3c30d800ab4e4f2ca162659a19cca9ae2021-12-02T01:35:41ZNegative Transpulmonary Pressure Disrupts Airway Morphogenesis by Suppressing Fgf102296-634X10.3389/fcell.2021.725785https://doaj.org/article/3c30d800ab4e4f2ca162659a19cca9ae2021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.725785/fullhttps://doaj.org/toc/2296-634XMechanical forces are increasingly recognized as important determinants of cell and tissue phenotype and also appear to play a critical role in organ development. During the fetal stages of lung morphogenesis, the pressure of the fluid within the lumen of the airways is higher than that within the chest cavity, resulting in a positive transpulmonary pressure. Several congenital defects decrease or reverse transpulmonary pressure across the developing airways and are associated with a reduced number of branches and a correspondingly underdeveloped lung that is insufficient for gas exchange after birth. The small size of the early pseudoglandular stage lung and its relative inaccessibility in utero have precluded experimental investigation of the effects of transpulmonary pressure on early branching morphogenesis. Here, we present a simple culture model to explore the effects of negative transpulmonary pressure on development of the embryonic airways. We found that negative transpulmonary pressure decreases branching, and that it does so in part by altering the expression of fibroblast growth factor 10 (Fgf10). The morphogenesis of lungs maintained under negative transpulmonary pressure can be rescued by supplementing the culture medium with exogenous FGF10. These data suggest that Fgf10 expression is regulated by mechanical stress in the developing airways. Understanding the mechanical signaling pathways that connect transpulmonary pressure to FGF10 can lead to the establishment of novel non-surgical approaches for ameliorating congenital lung defects.Alice E. StantonKatharine GoodwinAswin SundarakrishnanJacob M. JasloveJason P. GleghornAmira L. PavlovichCeleste M. NelsonCeleste M. NelsonFrontiers Media S.A.articletissue morphodynamicslung liquidmechanical stressmechanotransductionpulmonary hypoplasiacongenital diaphragmatic hernia (CDH)Biology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	tissue morphodynamics lung liquid mechanical stress mechanotransduction pulmonary hypoplasia congenital diaphragmatic hernia (CDH) Biology (General) QH301-705.5
spellingShingle	tissue morphodynamics lung liquid mechanical stress mechanotransduction pulmonary hypoplasia congenital diaphragmatic hernia (CDH) Biology (General) QH301-705.5 Alice E. Stanton Katharine Goodwin Aswin Sundarakrishnan Jacob M. Jaslove Jason P. Gleghorn Amira L. Pavlovich Celeste M. Nelson Celeste M. Nelson Negative Transpulmonary Pressure Disrupts Airway Morphogenesis by Suppressing Fgf10
description	Mechanical forces are increasingly recognized as important determinants of cell and tissue phenotype and also appear to play a critical role in organ development. During the fetal stages of lung morphogenesis, the pressure of the fluid within the lumen of the airways is higher than that within the chest cavity, resulting in a positive transpulmonary pressure. Several congenital defects decrease or reverse transpulmonary pressure across the developing airways and are associated with a reduced number of branches and a correspondingly underdeveloped lung that is insufficient for gas exchange after birth. The small size of the early pseudoglandular stage lung and its relative inaccessibility in utero have precluded experimental investigation of the effects of transpulmonary pressure on early branching morphogenesis. Here, we present a simple culture model to explore the effects of negative transpulmonary pressure on development of the embryonic airways. We found that negative transpulmonary pressure decreases branching, and that it does so in part by altering the expression of fibroblast growth factor 10 (Fgf10). The morphogenesis of lungs maintained under negative transpulmonary pressure can be rescued by supplementing the culture medium with exogenous FGF10. These data suggest that Fgf10 expression is regulated by mechanical stress in the developing airways. Understanding the mechanical signaling pathways that connect transpulmonary pressure to FGF10 can lead to the establishment of novel non-surgical approaches for ameliorating congenital lung defects.
format	article
author	Alice E. Stanton Katharine Goodwin Aswin Sundarakrishnan Jacob M. Jaslove Jason P. Gleghorn Amira L. Pavlovich Celeste M. Nelson Celeste M. Nelson
author_facet	Alice E. Stanton Katharine Goodwin Aswin Sundarakrishnan Jacob M. Jaslove Jason P. Gleghorn Amira L. Pavlovich Celeste M. Nelson Celeste M. Nelson
author_sort	Alice E. Stanton
title	Negative Transpulmonary Pressure Disrupts Airway Morphogenesis by Suppressing Fgf10
title_short	Negative Transpulmonary Pressure Disrupts Airway Morphogenesis by Suppressing Fgf10
title_full	Negative Transpulmonary Pressure Disrupts Airway Morphogenesis by Suppressing Fgf10
title_fullStr	Negative Transpulmonary Pressure Disrupts Airway Morphogenesis by Suppressing Fgf10
title_full_unstemmed	Negative Transpulmonary Pressure Disrupts Airway Morphogenesis by Suppressing Fgf10
title_sort	negative transpulmonary pressure disrupts airway morphogenesis by suppressing fgf10
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/3c30d800ab4e4f2ca162659a19cca9ae
work_keys_str_mv	AT aliceestanton negativetranspulmonarypressuredisruptsairwaymorphogenesisbysuppressingfgf10 AT katharinegoodwin negativetranspulmonarypressuredisruptsairwaymorphogenesisbysuppressingfgf10 AT aswinsundarakrishnan negativetranspulmonarypressuredisruptsairwaymorphogenesisbysuppressingfgf10 AT jacobmjaslove negativetranspulmonarypressuredisruptsairwaymorphogenesisbysuppressingfgf10 AT jasonpgleghorn negativetranspulmonarypressuredisruptsairwaymorphogenesisbysuppressingfgf10 AT amiralpavlovich negativetranspulmonarypressuredisruptsairwaymorphogenesisbysuppressingfgf10 AT celestemnelson negativetranspulmonarypressuredisruptsairwaymorphogenesisbysuppressingfgf10 AT celestemnelson negativetranspulmonarypressuredisruptsairwaymorphogenesisbysuppressingfgf10
_version_	1718402951041515520

Negative Transpulmonary Pressure Disrupts Airway Morphogenesis by Suppressing Fgf10

Ejemplares similares