gdf11 is required for pronephros/cloaca development through targeting TGF-β signaling

Abstract The kidney is a vital organ responsible for removing toxins, producing urine, and regulating homeostasis. Developmental defects in the kidney lead to various congenital abnormalities that impair renal function. Gdf11, a member of the transforming growth factor β family, is associated with n...

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Main Authors: Xinning Tian, Wantao Yao, Jin Tan, Zhangle Hu, Jingwen Liu
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-92571-y
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author Xinning Tian
Wantao Yao
Jin Tan
Zhangle Hu
Jingwen Liu
author_facet Xinning Tian
Wantao Yao
Jin Tan
Zhangle Hu
Jingwen Liu
author_sort Xinning Tian
collection DOAJ
description Abstract The kidney is a vital organ responsible for removing toxins, producing urine, and regulating homeostasis. Developmental defects in the kidney lead to various congenital abnormalities that impair renal function. Gdf11, a member of the transforming growth factor β family, is associated with numerous renal abnormalities. In the early developmental stage, the pronephric duct and hindgut open into the cloaca, and Gdf11 shows significant expression in the hindgut of mice. However, the molecular and cellular roles of gdf11 in kidney and cloaca organogenesis remain unclear. Our study revealed that pronephros and cloaca formation were significantly disrupted upon gdf11 deletion or knockdown in zebrafish. Additionally, we found that the TGF-β pathway acts downstream of Gdf11 in promoting pronephros and cloaca development. Treatment with a TGF-β small molecule activator partially rescued the pronephros and cloaca developmental defects observed in gdf11 −/− mutants. In summary, our findings provide strong evidence of a critical link between pronephros/cloaca formation and TGF-β signaling mediated by Gdf11. Our study also provides new insight into diseases related to renal and cloaca development.
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issn 2045-2322
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spelling doaj-art-356a2b15808641abb4a3a22365b4716d2025-08-20T01:57:45ZengNature PortfolioScientific Reports2045-23222025-03-0115111310.1038/s41598-025-92571-ygdf11 is required for pronephros/cloaca development through targeting TGF-β signalingXinning Tian0Wantao Yao1Jin Tan2Zhangle Hu3Jingwen Liu4Department of Cardiology, the Second Affiliated Hospital of Anhui Medical UniversityDepartment of Cardiology, the Second Affiliated Hospital of Anhui Medical UniversityDepartment of Cardiology, the Second Affiliated Hospital of Anhui Medical UniversityDepartment of Cardiology, the Second Affiliated Hospital of Anhui Medical UniversityDepartment of Cardiology, the Second Affiliated Hospital of Anhui Medical UniversityAbstract The kidney is a vital organ responsible for removing toxins, producing urine, and regulating homeostasis. Developmental defects in the kidney lead to various congenital abnormalities that impair renal function. Gdf11, a member of the transforming growth factor β family, is associated with numerous renal abnormalities. In the early developmental stage, the pronephric duct and hindgut open into the cloaca, and Gdf11 shows significant expression in the hindgut of mice. However, the molecular and cellular roles of gdf11 in kidney and cloaca organogenesis remain unclear. Our study revealed that pronephros and cloaca formation were significantly disrupted upon gdf11 deletion or knockdown in zebrafish. Additionally, we found that the TGF-β pathway acts downstream of Gdf11 in promoting pronephros and cloaca development. Treatment with a TGF-β small molecule activator partially rescued the pronephros and cloaca developmental defects observed in gdf11 −/− mutants. In summary, our findings provide strong evidence of a critical link between pronephros/cloaca formation and TGF-β signaling mediated by Gdf11. Our study also provides new insight into diseases related to renal and cloaca development.https://doi.org/10.1038/s41598-025-92571-yGdf11ZebrafishTGF-βPronephrosCloaca
spellingShingle Xinning Tian
Wantao Yao
Jin Tan
Zhangle Hu
Jingwen Liu
gdf11 is required for pronephros/cloaca development through targeting TGF-β signaling
Scientific Reports
Gdf11
Zebrafish
TGF-β
Pronephros
Cloaca
title gdf11 is required for pronephros/cloaca development through targeting TGF-β signaling
title_full gdf11 is required for pronephros/cloaca development through targeting TGF-β signaling
title_fullStr gdf11 is required for pronephros/cloaca development through targeting TGF-β signaling
title_full_unstemmed gdf11 is required for pronephros/cloaca development through targeting TGF-β signaling
title_short gdf11 is required for pronephros/cloaca development through targeting TGF-β signaling
title_sort gdf11 is required for pronephros cloaca development through targeting tgf β signaling
topic Gdf11
Zebrafish
TGF-β
Pronephros
Cloaca
url https://doi.org/10.1038/s41598-025-92571-y
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