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The zebrafish paralog six2b is required for early proximal pronephros morphogenesis

The transcription factor Six2 plays a crucial role in maintaining self-renewing nephron progenitor cap mesenchyme (CM) during metanephric kidney development. In mouse and human, expression at single-cell resolution has detected Six2 in cells as they leave the CM pool and differentiate. The role Six2...

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Autores principales: Belcher, Beau, Vestal, Justin, Lane, Samuel, Kell, Margaret, Smith, Luke, Camarata, Troy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10640633/
https://www.ncbi.nlm.nih.gov/pubmed/37952044
http://dx.doi.org/10.1038/s41598-023-47046-3
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author Belcher, Beau
Vestal, Justin
Lane, Samuel
Kell, Margaret
Smith, Luke
Camarata, Troy
author_facet Belcher, Beau
Vestal, Justin
Lane, Samuel
Kell, Margaret
Smith, Luke
Camarata, Troy
author_sort Belcher, Beau
collection PubMed
description The transcription factor Six2 plays a crucial role in maintaining self-renewing nephron progenitor cap mesenchyme (CM) during metanephric kidney development. In mouse and human, expression at single-cell resolution has detected Six2 in cells as they leave the CM pool and differentiate. The role Six2 may play in these cells as they differentiate remains unknown. Here, we took advantage of the zebrafish pronephric kidney which forms directly from intermediate mesoderm to test six2b function during pronephric tubule development and differentiation. Expression of six2b during early zebrafish development was consistent with a role in pronephros formation. Using morpholino knock-down and CRISPR/Cas9 mutagenesis, we show a functional role for six2b in the development of proximal elements of the pronephros. By 48 h post-fertilization, six2b morphants and mutants showed disrupted pronephric tubule morphogenesis. We observed a lower-than-expected frequency of phenotypes in six2b stable genetic mutants suggesting compensation. Supporting this, we detected increased expression of six2a in six2b stable mutant embryos. To further confirm six2b function, F(0) crispant embryos were analyzed and displayed similar phenotypes as morphants and stable mutants. Together our data suggests a conserved role for Six2 during nephrogenesis and a role in the morphogenesis of the proximal tubule.
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spelling pubmed-106406332023-11-11 The zebrafish paralog six2b is required for early proximal pronephros morphogenesis Belcher, Beau Vestal, Justin Lane, Samuel Kell, Margaret Smith, Luke Camarata, Troy Sci Rep Article The transcription factor Six2 plays a crucial role in maintaining self-renewing nephron progenitor cap mesenchyme (CM) during metanephric kidney development. In mouse and human, expression at single-cell resolution has detected Six2 in cells as they leave the CM pool and differentiate. The role Six2 may play in these cells as they differentiate remains unknown. Here, we took advantage of the zebrafish pronephric kidney which forms directly from intermediate mesoderm to test six2b function during pronephric tubule development and differentiation. Expression of six2b during early zebrafish development was consistent with a role in pronephros formation. Using morpholino knock-down and CRISPR/Cas9 mutagenesis, we show a functional role for six2b in the development of proximal elements of the pronephros. By 48 h post-fertilization, six2b morphants and mutants showed disrupted pronephric tubule morphogenesis. We observed a lower-than-expected frequency of phenotypes in six2b stable genetic mutants suggesting compensation. Supporting this, we detected increased expression of six2a in six2b stable mutant embryos. To further confirm six2b function, F(0) crispant embryos were analyzed and displayed similar phenotypes as morphants and stable mutants. Together our data suggests a conserved role for Six2 during nephrogenesis and a role in the morphogenesis of the proximal tubule. Nature Publishing Group UK 2023-11-11 /pmc/articles/PMC10640633/ /pubmed/37952044 http://dx.doi.org/10.1038/s41598-023-47046-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Belcher, Beau
Vestal, Justin
Lane, Samuel
Kell, Margaret
Smith, Luke
Camarata, Troy
The zebrafish paralog six2b is required for early proximal pronephros morphogenesis
title The zebrafish paralog six2b is required for early proximal pronephros morphogenesis
title_full The zebrafish paralog six2b is required for early proximal pronephros morphogenesis
title_fullStr The zebrafish paralog six2b is required for early proximal pronephros morphogenesis
title_full_unstemmed The zebrafish paralog six2b is required for early proximal pronephros morphogenesis
title_short The zebrafish paralog six2b is required for early proximal pronephros morphogenesis
title_sort zebrafish paralog six2b is required for early proximal pronephros morphogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10640633/
https://www.ncbi.nlm.nih.gov/pubmed/37952044
http://dx.doi.org/10.1038/s41598-023-47046-3
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