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Hedgehog regulation of epithelial cell state and morphogenesis in the larynx

The larynx enables speech while regulating swallowing and respiration. Larynx function hinges on the laryngeal epithelium which originates as part of the anterior foregut and undergoes extensive remodeling to separate from the esophagus and form vocal folds that interface with the adjacent trachea....

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Autores principales: Ramachandran, Janani, Zhou, Weiqiang, Bardenhagen, Anna E, Nasr, Talia, Yates, Ellen R, Zorn, Aaron M, Ji, Hongkai, Vokes, Steven A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9718526/
https://www.ncbi.nlm.nih.gov/pubmed/36398878
http://dx.doi.org/10.7554/eLife.77055
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author Ramachandran, Janani
Zhou, Weiqiang
Bardenhagen, Anna E
Nasr, Talia
Yates, Ellen R
Zorn, Aaron M
Ji, Hongkai
Vokes, Steven A
author_facet Ramachandran, Janani
Zhou, Weiqiang
Bardenhagen, Anna E
Nasr, Talia
Yates, Ellen R
Zorn, Aaron M
Ji, Hongkai
Vokes, Steven A
author_sort Ramachandran, Janani
collection PubMed
description The larynx enables speech while regulating swallowing and respiration. Larynx function hinges on the laryngeal epithelium which originates as part of the anterior foregut and undergoes extensive remodeling to separate from the esophagus and form vocal folds that interface with the adjacent trachea. Here we find that sonic hedgehog (SHH) is essential for epithelial integrity in the mouse larynx as well as the anterior foregut. During larynx-esophageal separation, low Shh expression marks specific domains of actively remodeling epithelium that undergo an epithelial-to-mesenchymal transition (EMT) characterized by the induction of N-Cadherin and movement of cells out of the epithelial layer. Consistent with a role for SHH signaling in regulating this process, Shh mutants undergo an abnormal EMT throughout the anterior foregut and larynx, marked by a cadherin switch, movement out of the epithelial layer and cell death. Unexpectedly, Shh mutant epithelial cells are replaced by a new population of FOXA2-negative cells that likely derive from adjacent pouch tissues and form a rudimentary epithelium. These findings have important implications for interpreting the etiology of HH-dependent birth defects within the foregut. We propose that SHH signaling has a default role in maintaining epithelial identity throughout the anterior foregut and that regionalized reductions in SHH trigger epithelial remodeling.
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spelling pubmed-97185262022-12-03 Hedgehog regulation of epithelial cell state and morphogenesis in the larynx Ramachandran, Janani Zhou, Weiqiang Bardenhagen, Anna E Nasr, Talia Yates, Ellen R Zorn, Aaron M Ji, Hongkai Vokes, Steven A eLife Developmental Biology The larynx enables speech while regulating swallowing and respiration. Larynx function hinges on the laryngeal epithelium which originates as part of the anterior foregut and undergoes extensive remodeling to separate from the esophagus and form vocal folds that interface with the adjacent trachea. Here we find that sonic hedgehog (SHH) is essential for epithelial integrity in the mouse larynx as well as the anterior foregut. During larynx-esophageal separation, low Shh expression marks specific domains of actively remodeling epithelium that undergo an epithelial-to-mesenchymal transition (EMT) characterized by the induction of N-Cadherin and movement of cells out of the epithelial layer. Consistent with a role for SHH signaling in regulating this process, Shh mutants undergo an abnormal EMT throughout the anterior foregut and larynx, marked by a cadherin switch, movement out of the epithelial layer and cell death. Unexpectedly, Shh mutant epithelial cells are replaced by a new population of FOXA2-negative cells that likely derive from adjacent pouch tissues and form a rudimentary epithelium. These findings have important implications for interpreting the etiology of HH-dependent birth defects within the foregut. We propose that SHH signaling has a default role in maintaining epithelial identity throughout the anterior foregut and that regionalized reductions in SHH trigger epithelial remodeling. eLife Sciences Publications, Ltd 2022-11-18 /pmc/articles/PMC9718526/ /pubmed/36398878 http://dx.doi.org/10.7554/eLife.77055 Text en © 2022, Ramachandran et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Developmental Biology
Ramachandran, Janani
Zhou, Weiqiang
Bardenhagen, Anna E
Nasr, Talia
Yates, Ellen R
Zorn, Aaron M
Ji, Hongkai
Vokes, Steven A
Hedgehog regulation of epithelial cell state and morphogenesis in the larynx
title Hedgehog regulation of epithelial cell state and morphogenesis in the larynx
title_full Hedgehog regulation of epithelial cell state and morphogenesis in the larynx
title_fullStr Hedgehog regulation of epithelial cell state and morphogenesis in the larynx
title_full_unstemmed Hedgehog regulation of epithelial cell state and morphogenesis in the larynx
title_short Hedgehog regulation of epithelial cell state and morphogenesis in the larynx
title_sort hedgehog regulation of epithelial cell state and morphogenesis in the larynx
topic Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9718526/
https://www.ncbi.nlm.nih.gov/pubmed/36398878
http://dx.doi.org/10.7554/eLife.77055
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