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LIM homeodomain transcription factor Isl1 affects urethral epithelium differentiation and apoptosis via Shh

Urethral hypoplasia, including failure of urethral tube closure, is one of the common phenotypes observed in hereditary human disorders, the mechanism of which remains unclear. The present study was thus designed to study the expression, functions, and related mechanisms of the LIM homeobox transcri...

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Autores principales: Su, Tiantian, Liu, Hui, Zhang, Di, Xu, Guojin, Liu, Jiali, Evans, Sylvia M., Pan, Jirong, Cui, Sheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763423/
https://www.ncbi.nlm.nih.gov/pubmed/31558700
http://dx.doi.org/10.1038/s41419-019-1952-z
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author Su, Tiantian
Liu, Hui
Zhang, Di
Xu, Guojin
Liu, Jiali
Evans, Sylvia M.
Pan, Jirong
Cui, Sheng
author_facet Su, Tiantian
Liu, Hui
Zhang, Di
Xu, Guojin
Liu, Jiali
Evans, Sylvia M.
Pan, Jirong
Cui, Sheng
author_sort Su, Tiantian
collection PubMed
description Urethral hypoplasia, including failure of urethral tube closure, is one of the common phenotypes observed in hereditary human disorders, the mechanism of which remains unclear. The present study was thus designed to study the expression, functions, and related mechanisms of the LIM homeobox transcription factor Isl1 throughout mouse urethral development. Results showed that Isl1 was highly expressed in urethral epithelial cells and mesenchymal cells of the genital tubercle (GT). Functional studies were carried out by utilizing the tamoxifen-inducible Isl1-knockout mouse model. Histological and morphological results indicated that Isl1 deletion caused urethral hypoplasia and inhibited maturation of the complex urethral epithelium. In addition, we show that Isl1-deleted mice failed to maintain the progenitor cell population required for renewal of urethral epithelium during tubular morphogenesis and exhibited significantly increased cell death within the urethra. Dual-Luciferase reporter assays and yeast one-hybrid assays showed that ISL1 was essential for normal urethral development by directly targeting the Shh gene. Collectively, results presented here demonstrated that Isl1 plays a crucial role in mouse urethral development, thus increasing our potential for understanding the mechanistic basis of hereditary urethral hypoplasia.
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spelling pubmed-67634232019-09-27 LIM homeodomain transcription factor Isl1 affects urethral epithelium differentiation and apoptosis via Shh Su, Tiantian Liu, Hui Zhang, Di Xu, Guojin Liu, Jiali Evans, Sylvia M. Pan, Jirong Cui, Sheng Cell Death Dis Article Urethral hypoplasia, including failure of urethral tube closure, is one of the common phenotypes observed in hereditary human disorders, the mechanism of which remains unclear. The present study was thus designed to study the expression, functions, and related mechanisms of the LIM homeobox transcription factor Isl1 throughout mouse urethral development. Results showed that Isl1 was highly expressed in urethral epithelial cells and mesenchymal cells of the genital tubercle (GT). Functional studies were carried out by utilizing the tamoxifen-inducible Isl1-knockout mouse model. Histological and morphological results indicated that Isl1 deletion caused urethral hypoplasia and inhibited maturation of the complex urethral epithelium. In addition, we show that Isl1-deleted mice failed to maintain the progenitor cell population required for renewal of urethral epithelium during tubular morphogenesis and exhibited significantly increased cell death within the urethra. Dual-Luciferase reporter assays and yeast one-hybrid assays showed that ISL1 was essential for normal urethral development by directly targeting the Shh gene. Collectively, results presented here demonstrated that Isl1 plays a crucial role in mouse urethral development, thus increasing our potential for understanding the mechanistic basis of hereditary urethral hypoplasia. Nature Publishing Group UK 2019-09-26 /pmc/articles/PMC6763423/ /pubmed/31558700 http://dx.doi.org/10.1038/s41419-019-1952-z Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Su, Tiantian
Liu, Hui
Zhang, Di
Xu, Guojin
Liu, Jiali
Evans, Sylvia M.
Pan, Jirong
Cui, Sheng
LIM homeodomain transcription factor Isl1 affects urethral epithelium differentiation and apoptosis via Shh
title LIM homeodomain transcription factor Isl1 affects urethral epithelium differentiation and apoptosis via Shh
title_full LIM homeodomain transcription factor Isl1 affects urethral epithelium differentiation and apoptosis via Shh
title_fullStr LIM homeodomain transcription factor Isl1 affects urethral epithelium differentiation and apoptosis via Shh
title_full_unstemmed LIM homeodomain transcription factor Isl1 affects urethral epithelium differentiation and apoptosis via Shh
title_short LIM homeodomain transcription factor Isl1 affects urethral epithelium differentiation and apoptosis via Shh
title_sort lim homeodomain transcription factor isl1 affects urethral epithelium differentiation and apoptosis via shh
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763423/
https://www.ncbi.nlm.nih.gov/pubmed/31558700
http://dx.doi.org/10.1038/s41419-019-1952-z
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