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Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor
The neural crest (NC) is an important multipotent embryonic cell population and its impaired specification leads to various developmental defects, often in an anteroposterior (A-P) axial level-specific manner. The mechanisms underlying the correct A-P regionalisation of human NC cells remain elusive...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536837/ https://www.ncbi.nlm.nih.gov/pubmed/36154671 http://dx.doi.org/10.7554/eLife.74263 |
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author | Gogolou, Antigoni Souilhol, Celine Granata, Ilaria Wymeersch, Filip J Manipur, Ichcha Wind, Matthew Frith, Thomas JR Guarini, Maria Bertero, Alessandro Bock, Christoph Halbritter, Florian Takasato, Minoru Guarracino, Mario R Tsakiridis, Anestis |
author_facet | Gogolou, Antigoni Souilhol, Celine Granata, Ilaria Wymeersch, Filip J Manipur, Ichcha Wind, Matthew Frith, Thomas JR Guarini, Maria Bertero, Alessandro Bock, Christoph Halbritter, Florian Takasato, Minoru Guarracino, Mario R Tsakiridis, Anestis |
author_sort | Gogolou, Antigoni |
collection | PubMed |
description | The neural crest (NC) is an important multipotent embryonic cell population and its impaired specification leads to various developmental defects, often in an anteroposterior (A-P) axial level-specific manner. The mechanisms underlying the correct A-P regionalisation of human NC cells remain elusive. Recent studies have indicated that trunk NC cells, the presumed precursors of childhood tumour neuroblastoma, are derived from neuromesodermal-potent progenitors of the postcranial body. Here we employ human embryonic stem cell differentiation to define how neuromesodermal progenitor (NMP)-derived NC cells acquire a posterior axial identity. We show that TBXT, a pro-mesodermal transcription factor, mediates early posterior NC/spinal cord regionalisation together with WNT signalling effectors. This occurs by TBXT-driven chromatin remodelling via its binding in key enhancers within HOX gene clusters and other posterior regulator-associated loci. This initial posteriorisation event is succeeded by a second phase of trunk HOX gene control that marks the differentiation of NMPs toward their TBXT-negative NC/spinal cord derivatives and relies predominantly on FGF signalling. Our work reveals a previously unknown role of TBXT in influencing posterior NC fate and points to the existence of temporally discrete, cell type-dependent modes of posterior axial identity control. |
format | Online Article Text |
id | pubmed-9536837 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-95368372022-10-07 Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor Gogolou, Antigoni Souilhol, Celine Granata, Ilaria Wymeersch, Filip J Manipur, Ichcha Wind, Matthew Frith, Thomas JR Guarini, Maria Bertero, Alessandro Bock, Christoph Halbritter, Florian Takasato, Minoru Guarracino, Mario R Tsakiridis, Anestis eLife Developmental Biology The neural crest (NC) is an important multipotent embryonic cell population and its impaired specification leads to various developmental defects, often in an anteroposterior (A-P) axial level-specific manner. The mechanisms underlying the correct A-P regionalisation of human NC cells remain elusive. Recent studies have indicated that trunk NC cells, the presumed precursors of childhood tumour neuroblastoma, are derived from neuromesodermal-potent progenitors of the postcranial body. Here we employ human embryonic stem cell differentiation to define how neuromesodermal progenitor (NMP)-derived NC cells acquire a posterior axial identity. We show that TBXT, a pro-mesodermal transcription factor, mediates early posterior NC/spinal cord regionalisation together with WNT signalling effectors. This occurs by TBXT-driven chromatin remodelling via its binding in key enhancers within HOX gene clusters and other posterior regulator-associated loci. This initial posteriorisation event is succeeded by a second phase of trunk HOX gene control that marks the differentiation of NMPs toward their TBXT-negative NC/spinal cord derivatives and relies predominantly on FGF signalling. Our work reveals a previously unknown role of TBXT in influencing posterior NC fate and points to the existence of temporally discrete, cell type-dependent modes of posterior axial identity control. eLife Sciences Publications, Ltd 2022-09-26 /pmc/articles/PMC9536837/ /pubmed/36154671 http://dx.doi.org/10.7554/eLife.74263 Text en © 2022, Gogolou 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 Gogolou, Antigoni Souilhol, Celine Granata, Ilaria Wymeersch, Filip J Manipur, Ichcha Wind, Matthew Frith, Thomas JR Guarini, Maria Bertero, Alessandro Bock, Christoph Halbritter, Florian Takasato, Minoru Guarracino, Mario R Tsakiridis, Anestis Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor |
title | Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor |
title_full | Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor |
title_fullStr | Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor |
title_full_unstemmed | Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor |
title_short | Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor |
title_sort | early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor |
topic | Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536837/ https://www.ncbi.nlm.nih.gov/pubmed/36154671 http://dx.doi.org/10.7554/eLife.74263 |
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