Anxa4 mediated airway progenitor cell migration promotes distal epithelial cell fate specification

Abstract Genetic studies have shown that FGF10/FGFR2 signaling is required for airway branching morphogenesis and FGF10 functions as a chemoattractant factor for distal epithelial cells during lung development. However, the detail downstream cellular and molecular mechanisms have not been fully char...

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Autores principales:	Kewu Jiang, Zan Tang, Juan Li, Fengchao Wang, Nan Tang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Airway Progenitor Cells Cell Clefts Endodermal Bud Distal Airways Lung Endoderm Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8e5eb763830e4f5c9f0840757052e6fb
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spelling	oai:doaj.org-article:8e5eb763830e4f5c9f0840757052e6fb2021-12-02T15:08:00ZAnxa4 mediated airway progenitor cell migration promotes distal epithelial cell fate specification10.1038/s41598-018-32494-z2045-2322https://doaj.org/article/8e5eb763830e4f5c9f0840757052e6fb2018-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-32494-zhttps://doaj.org/toc/2045-2322Abstract Genetic studies have shown that FGF10/FGFR2 signaling is required for airway branching morphogenesis and FGF10 functions as a chemoattractant factor for distal epithelial cells during lung development. However, the detail downstream cellular and molecular mechanisms have not been fully characterized. Using live imaging of ex vivo cultured lungs, we found that tip airway epithelial progenitor cells migrate faster than cleft cells during airway bud formation and this migration process is controlled by FGFR2-mediated ERK1/2 signaling. Additionally, we found that airway progenitor cells that migrate faster tend to become distal airway progenitor cells. We identified that Anxa4 is a downstream target of ERK1/2 signaling. Anxa4 −/− airway epithelial cells exhibit a “lag-behind” behavior and tend to stay at the stalk airways. Moreover, we found that Anxa4-overexpressing cells tend to migrate to the bud tips. Finally, we demonstrated that Anxa4 functions redundantly with Anxa1 and Anxa6 in regulating endoderm budding process. Our study demonstrates that ERK1/2/Anxa4 signaling plays a role in promoting the migration of airway epithelial progenitor cells to distal airway tips and ensuring their distal cell fate.Kewu JiangZan TangJuan LiFengchao WangNan TangNature PortfolioarticleAirway Progenitor CellsCell CleftsEndodermal BudDistal AirwaysLung EndodermMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Airway Progenitor Cells Cell Clefts Endodermal Bud Distal Airways Lung Endoderm Medicine R Science Q
spellingShingle	Airway Progenitor Cells Cell Clefts Endodermal Bud Distal Airways Lung Endoderm Medicine R Science Q Kewu Jiang Zan Tang Juan Li Fengchao Wang Nan Tang Anxa4 mediated airway progenitor cell migration promotes distal epithelial cell fate specification
description	Abstract Genetic studies have shown that FGF10/FGFR2 signaling is required for airway branching morphogenesis and FGF10 functions as a chemoattractant factor for distal epithelial cells during lung development. However, the detail downstream cellular and molecular mechanisms have not been fully characterized. Using live imaging of ex vivo cultured lungs, we found that tip airway epithelial progenitor cells migrate faster than cleft cells during airway bud formation and this migration process is controlled by FGFR2-mediated ERK1/2 signaling. Additionally, we found that airway progenitor cells that migrate faster tend to become distal airway progenitor cells. We identified that Anxa4 is a downstream target of ERK1/2 signaling. Anxa4 −/− airway epithelial cells exhibit a “lag-behind” behavior and tend to stay at the stalk airways. Moreover, we found that Anxa4-overexpressing cells tend to migrate to the bud tips. Finally, we demonstrated that Anxa4 functions redundantly with Anxa1 and Anxa6 in regulating endoderm budding process. Our study demonstrates that ERK1/2/Anxa4 signaling plays a role in promoting the migration of airway epithelial progenitor cells to distal airway tips and ensuring their distal cell fate.
format	article
author	Kewu Jiang Zan Tang Juan Li Fengchao Wang Nan Tang
author_facet	Kewu Jiang Zan Tang Juan Li Fengchao Wang Nan Tang
author_sort	Kewu Jiang
title	Anxa4 mediated airway progenitor cell migration promotes distal epithelial cell fate specification
title_short	Anxa4 mediated airway progenitor cell migration promotes distal epithelial cell fate specification
title_full	Anxa4 mediated airway progenitor cell migration promotes distal epithelial cell fate specification
title_fullStr	Anxa4 mediated airway progenitor cell migration promotes distal epithelial cell fate specification
title_full_unstemmed	Anxa4 mediated airway progenitor cell migration promotes distal epithelial cell fate specification
title_sort	anxa4 mediated airway progenitor cell migration promotes distal epithelial cell fate specification
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/8e5eb763830e4f5c9f0840757052e6fb
work_keys_str_mv	AT kewujiang anxa4mediatedairwayprogenitorcellmigrationpromotesdistalepithelialcellfatespecification AT zantang anxa4mediatedairwayprogenitorcellmigrationpromotesdistalepithelialcellfatespecification AT juanli anxa4mediatedairwayprogenitorcellmigrationpromotesdistalepithelialcellfatespecification AT fengchaowang anxa4mediatedairwayprogenitorcellmigrationpromotesdistalepithelialcellfatespecification AT nantang anxa4mediatedairwayprogenitorcellmigrationpromotesdistalepithelialcellfatespecification
_version_	1718388330140270592

Anxa4 mediated airway progenitor cell migration promotes distal epithelial cell fate specification

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