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ISL1 regulates lung branching morphogenesis via Shh signaling pathway
Lung branching morphogenesis relies on a complex coordination of multiple signaling pathways and transcription factors. Here, we found that ablation of the LIM homeodomain transcription factor Islet1 (Isl1) in lung epithelium resulted in defective branching morphogenesis and incomplete formation of...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406864/ https://www.ncbi.nlm.nih.gov/pubmed/37442233 http://dx.doi.org/10.1016/j.jbc.2023.105034 |
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author | Huang, Ruiqi Zhang, Chujing Zheng, Yuting Zhang, Wei Huang, Huarong Qiu, Mengsheng Li, Jianying Li, Feixue |
author_facet | Huang, Ruiqi Zhang, Chujing Zheng, Yuting Zhang, Wei Huang, Huarong Qiu, Mengsheng Li, Jianying Li, Feixue |
author_sort | Huang, Ruiqi |
collection | PubMed |
description | Lung branching morphogenesis relies on a complex coordination of multiple signaling pathways and transcription factors. Here, we found that ablation of the LIM homeodomain transcription factor Islet1 (Isl1) in lung epithelium resulted in defective branching morphogenesis and incomplete formation of five lobes. A reduction in mesenchymal cell proliferation was observed in Isl1(ShhCre) lungs. There was no difference in apoptosis between the wild-type (Shh(Cre)) and Isl1(ShhCre) embryos. RNA-Seq and in situ hybridization analysis showed that Shh, Ptch1, Sox9, Irx1, Irx2, Tbx2, and Tbx3 were downregulated in the lungs of Isl1(ShhCre) embryos. ChIP assay implied the Shh gene served as a direct target of ISL1, since the transcription factor ISL1 could bind to the Shh epithelial enhancer sequence (MACS1). Also, activation of the Hedgehog pathway via ectopic gene expression rescued the defects caused by Isl1 ablation, confirming the genetic integration of Hedgehog signaling. In conclusion, our works suggest that epithelial Isl1 regulates lung branching morphogenesis through administrating the Shh signaling mediated epithelial-mesenchymal communications. |
format | Online Article Text |
id | pubmed-10406864 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-104068642023-08-09 ISL1 regulates lung branching morphogenesis via Shh signaling pathway Huang, Ruiqi Zhang, Chujing Zheng, Yuting Zhang, Wei Huang, Huarong Qiu, Mengsheng Li, Jianying Li, Feixue J Biol Chem Research Article Lung branching morphogenesis relies on a complex coordination of multiple signaling pathways and transcription factors. Here, we found that ablation of the LIM homeodomain transcription factor Islet1 (Isl1) in lung epithelium resulted in defective branching morphogenesis and incomplete formation of five lobes. A reduction in mesenchymal cell proliferation was observed in Isl1(ShhCre) lungs. There was no difference in apoptosis between the wild-type (Shh(Cre)) and Isl1(ShhCre) embryos. RNA-Seq and in situ hybridization analysis showed that Shh, Ptch1, Sox9, Irx1, Irx2, Tbx2, and Tbx3 were downregulated in the lungs of Isl1(ShhCre) embryos. ChIP assay implied the Shh gene served as a direct target of ISL1, since the transcription factor ISL1 could bind to the Shh epithelial enhancer sequence (MACS1). Also, activation of the Hedgehog pathway via ectopic gene expression rescued the defects caused by Isl1 ablation, confirming the genetic integration of Hedgehog signaling. In conclusion, our works suggest that epithelial Isl1 regulates lung branching morphogenesis through administrating the Shh signaling mediated epithelial-mesenchymal communications. American Society for Biochemistry and Molecular Biology 2023-07-11 /pmc/articles/PMC10406864/ /pubmed/37442233 http://dx.doi.org/10.1016/j.jbc.2023.105034 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Article Huang, Ruiqi Zhang, Chujing Zheng, Yuting Zhang, Wei Huang, Huarong Qiu, Mengsheng Li, Jianying Li, Feixue ISL1 regulates lung branching morphogenesis via Shh signaling pathway |
title | ISL1 regulates lung branching morphogenesis via Shh signaling pathway |
title_full | ISL1 regulates lung branching morphogenesis via Shh signaling pathway |
title_fullStr | ISL1 regulates lung branching morphogenesis via Shh signaling pathway |
title_full_unstemmed | ISL1 regulates lung branching morphogenesis via Shh signaling pathway |
title_short | ISL1 regulates lung branching morphogenesis via Shh signaling pathway |
title_sort | isl1 regulates lung branching morphogenesis via shh signaling pathway |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10406864/ https://www.ncbi.nlm.nih.gov/pubmed/37442233 http://dx.doi.org/10.1016/j.jbc.2023.105034 |
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