Non-canonical Wnt signaling promotes epithelial fluidization in the repairing airway

Abstract Concerted migration of basal stem cells (BCs) in the airway, also known as epithelial fluidization, has been implicated in epithelial repair after injury. How BC migration is regulated, and how it influences the success of epithelial repair, remains unclear. Here we have identified non-cano...

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Main Authors: Daniel Jun-Kit Hu, Xiaoyu Tracy Cai, Jesse Simons, Jina Yun, Justin Elstrott, Heinrich Jasper
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-59320-1
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author Daniel Jun-Kit Hu
Xiaoyu Tracy Cai
Jesse Simons
Jina Yun
Justin Elstrott
Heinrich Jasper
author_facet Daniel Jun-Kit Hu
Xiaoyu Tracy Cai
Jesse Simons
Jina Yun
Justin Elstrott
Heinrich Jasper
author_sort Daniel Jun-Kit Hu
collection DOAJ
description Abstract Concerted migration of basal stem cells (BCs) in the airway, also known as epithelial fluidization, has been implicated in epithelial repair after injury. How BC migration is regulated, and how it influences the success of epithelial repair, remains unclear. Here we have identified non-canonical Wnt signaling through Ptk7, Fzd7, and YAP as a critical regulator of BC migration in the mouse trachea. Using live imaging and genetic studies in the mouse, we find that Ptk7 is required for the concerted movement of BCs after injury, and that this requirement extends to BC proliferation and subsequent restoration of epithelial homeostasis after injury. We demonstrate that Ptk7 exerts this function in conjunction with Wnt5a and Fzd7, and through YAP activation in BCs. Our data provide mechanistic insight into the regulation of epithelial repair in the airway.
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institution Kabale University
issn 2041-1723
language English
publishDate 2025-05-01
publisher Nature Portfolio
record_format Article
series Nature Communications
spelling doaj-art-4d8093d1e67d4c1ab4b8d921d1b85b6a2025-08-20T03:52:24ZengNature PortfolioNature Communications2041-17232025-05-0116111310.1038/s41467-025-59320-1Non-canonical Wnt signaling promotes epithelial fluidization in the repairing airwayDaniel Jun-Kit Hu0Xiaoyu Tracy Cai1Jesse Simons2Jina Yun3Justin Elstrott4Heinrich Jasper5Regenerative Medicine, Genentech Inc.Regenerative Medicine, Genentech Inc.Regenerative Medicine, Genentech Inc.Regenerative Medicine, Genentech Inc.Translational Imaging, Genentech Inc.Regenerative Medicine, Genentech Inc.Abstract Concerted migration of basal stem cells (BCs) in the airway, also known as epithelial fluidization, has been implicated in epithelial repair after injury. How BC migration is regulated, and how it influences the success of epithelial repair, remains unclear. Here we have identified non-canonical Wnt signaling through Ptk7, Fzd7, and YAP as a critical regulator of BC migration in the mouse trachea. Using live imaging and genetic studies in the mouse, we find that Ptk7 is required for the concerted movement of BCs after injury, and that this requirement extends to BC proliferation and subsequent restoration of epithelial homeostasis after injury. We demonstrate that Ptk7 exerts this function in conjunction with Wnt5a and Fzd7, and through YAP activation in BCs. Our data provide mechanistic insight into the regulation of epithelial repair in the airway.https://doi.org/10.1038/s41467-025-59320-1
spellingShingle Daniel Jun-Kit Hu
Xiaoyu Tracy Cai
Jesse Simons
Jina Yun
Justin Elstrott
Heinrich Jasper
Non-canonical Wnt signaling promotes epithelial fluidization in the repairing airway
Nature Communications
title Non-canonical Wnt signaling promotes epithelial fluidization in the repairing airway
title_full Non-canonical Wnt signaling promotes epithelial fluidization in the repairing airway
title_fullStr Non-canonical Wnt signaling promotes epithelial fluidization in the repairing airway
title_full_unstemmed Non-canonical Wnt signaling promotes epithelial fluidization in the repairing airway
title_short Non-canonical Wnt signaling promotes epithelial fluidization in the repairing airway
title_sort non canonical wnt signaling promotes epithelial fluidization in the repairing airway
url https://doi.org/10.1038/s41467-025-59320-1
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