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Secreted inhibitors drive the loss of regeneration competence in Xenopus limbs
Absence of a specialized wound epidermis is hypothesized to block limb regeneration in higher vertebrates. However, the factors preventing its formation in regeneration-incompetent animals are poorly understood. To characterize the endogenous molecular and cellular regulators of specialized wound ep...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217717/ https://www.ncbi.nlm.nih.gov/pubmed/34105722 http://dx.doi.org/10.1242/dev.199158 |
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author | Aztekin, Can Hiscock, Tom W. Gurdon, John Jullien, Jerome Marioni, John Simons, Benjamin David |
author_facet | Aztekin, Can Hiscock, Tom W. Gurdon, John Jullien, Jerome Marioni, John Simons, Benjamin David |
author_sort | Aztekin, Can |
collection | PubMed |
description | Absence of a specialized wound epidermis is hypothesized to block limb regeneration in higher vertebrates. However, the factors preventing its formation in regeneration-incompetent animals are poorly understood. To characterize the endogenous molecular and cellular regulators of specialized wound epidermis formation in Xenopus laevis tadpoles, and the loss of their regeneration competency during development, we used single-cell transcriptomics and ex vivo regenerating limb cultures. Transcriptomic analysis revealed that the specialized wound epidermis is not a novel cell state, but a re-deployment of the apical-ectodermal-ridge (AER) programme underlying limb development. Enrichment of secreted inhibitory factors, including Noggin, a morphogen expressed in developing cartilage/bone progenitor cells, are identified as key inhibitors of AER cell formation in regeneration-incompetent tadpoles. These factors can be overridden by Fgf10, which operates upstream of Noggin and blocks chondrogenesis. These results indicate that manipulation of the extracellular environment and/or chondrogenesis may provide a strategy to restore regeneration potential in higher vertebrates. |
format | Online Article Text |
id | pubmed-8217717 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-82177172021-07-08 Secreted inhibitors drive the loss of regeneration competence in Xenopus limbs Aztekin, Can Hiscock, Tom W. Gurdon, John Jullien, Jerome Marioni, John Simons, Benjamin David Development Stem Cells and Regeneration Absence of a specialized wound epidermis is hypothesized to block limb regeneration in higher vertebrates. However, the factors preventing its formation in regeneration-incompetent animals are poorly understood. To characterize the endogenous molecular and cellular regulators of specialized wound epidermis formation in Xenopus laevis tadpoles, and the loss of their regeneration competency during development, we used single-cell transcriptomics and ex vivo regenerating limb cultures. Transcriptomic analysis revealed that the specialized wound epidermis is not a novel cell state, but a re-deployment of the apical-ectodermal-ridge (AER) programme underlying limb development. Enrichment of secreted inhibitory factors, including Noggin, a morphogen expressed in developing cartilage/bone progenitor cells, are identified as key inhibitors of AER cell formation in regeneration-incompetent tadpoles. These factors can be overridden by Fgf10, which operates upstream of Noggin and blocks chondrogenesis. These results indicate that manipulation of the extracellular environment and/or chondrogenesis may provide a strategy to restore regeneration potential in higher vertebrates. The Company of Biologists Ltd 2021-06-09 /pmc/articles/PMC8217717/ /pubmed/34105722 http://dx.doi.org/10.1242/dev.199158 Text en © 2021. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Stem Cells and Regeneration Aztekin, Can Hiscock, Tom W. Gurdon, John Jullien, Jerome Marioni, John Simons, Benjamin David Secreted inhibitors drive the loss of regeneration competence in Xenopus limbs |
title | Secreted inhibitors drive the loss of regeneration competence in Xenopus limbs |
title_full | Secreted inhibitors drive the loss of regeneration competence in Xenopus limbs |
title_fullStr | Secreted inhibitors drive the loss of regeneration competence in Xenopus limbs |
title_full_unstemmed | Secreted inhibitors drive the loss of regeneration competence in Xenopus limbs |
title_short | Secreted inhibitors drive the loss of regeneration competence in Xenopus limbs |
title_sort | secreted inhibitors drive the loss of regeneration competence in xenopus limbs |
topic | Stem Cells and Regeneration |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217717/ https://www.ncbi.nlm.nih.gov/pubmed/34105722 http://dx.doi.org/10.1242/dev.199158 |
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