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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-09-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/74263 |
| _version_ | 1798028491022663680 |
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| author | Antigoni Gogolou Celine Souilhol Ilaria Granata Filip J Wymeersch Ichcha Manipur Matthew Wind Thomas JR Frith Maria Guarini Alessandro Bertero Christoph Bock Florian Halbritter Minoru Takasato Mario R Guarracino Anestis Tsakiridis |
| author_facet | Antigoni Gogolou Celine Souilhol Ilaria Granata Filip J Wymeersch Ichcha Manipur Matthew Wind Thomas JR Frith Maria Guarini Alessandro Bertero Christoph Bock Florian Halbritter Minoru Takasato Mario R Guarracino Anestis Tsakiridis |
| author_sort | Antigoni Gogolou |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T19:08:46Z |
| format | Article |
| id | doaj.art-c178b29048894e99a818b0f879f6c59f |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T19:08:46Z |
| publishDate | 2022-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-c178b29048894e99a818b0f879f6c59f2022-12-22T04:07:40ZengeLife Sciences Publications LtdeLife2050-084X2022-09-011110.7554/eLife.74263Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factorAntigoni Gogolou0Celine Souilhol1Ilaria Granata2Filip J Wymeersch3https://orcid.org/0000-0001-8999-4555Ichcha Manipur4Matthew Wind5Thomas JR Frith6Maria Guarini7Alessandro Bertero8Christoph Bock9https://orcid.org/0000-0001-6091-3088Florian Halbritter10Minoru Takasato11https://orcid.org/0000-0002-0458-7414Mario R Guarracino12Anestis Tsakiridis13https://orcid.org/0000-0002-2184-2990Centre for Stem Cell Biology, School of Biosciences, University of Sheffield, Sheffield, United Kingdom; Neuroscience Institute, The University of Sheffield, Western Bank, Sheffield, United KingdomCentre for Stem Cell Biology, School of Biosciences, University of Sheffield, Sheffield, United Kingdom; Neuroscience Institute, The University of Sheffield, Western Bank, Sheffield, United KingdomComputational and Data Science Laboratory, High Performance Computing and Networking Institute, National Research Council of Italy, Napoli, ItalyLaboratory for Human Organogenesis, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, JapanComputational and Data Science Laboratory, High Performance Computing and Networking Institute, National Research Council of Italy, Napoli, ItalyCentre for Stem Cell Biology, School of Biosciences, University of Sheffield, Sheffield, United Kingdom; Neuroscience Institute, The University of Sheffield, Western Bank, Sheffield, United KingdomCentre for Stem Cell Biology, School of Biosciences, University of Sheffield, Sheffield, United Kingdom; Neuroscience Institute, The University of Sheffield, Western Bank, Sheffield, United KingdomCeMM Research Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, AustriaMolecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, ItalyCeMM Research Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria; Institute of Artificial Intelligence, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, AustriaSt. Anna Children's Cancer Research Institute, Vienna, AustriaLaboratory for Human Organogenesis, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Japan; Laboratory of Molecular Cell Biology and Development, Department of Animal Development and Physiology, Graduate School of Bio-studies, Kyoto University, Kyoto, JapanUniversity of Cassino and Southern Lazio, Cassino, ItalyCentre for Stem Cell Biology, School of Biosciences, University of Sheffield, Sheffield, United Kingdom; Neuroscience Institute, The University of Sheffield, Western Bank, Sheffield, United KingdomThe 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.https://elifesciences.org/articles/74263axial identitybrachyuryHoxneuromesodermal progenitorsneural crestembryonic stem cells |
| spellingShingle | Antigoni Gogolou Celine Souilhol Ilaria Granata Filip J Wymeersch Ichcha Manipur Matthew Wind Thomas JR Frith Maria Guarini Alessandro Bertero Christoph Bock Florian Halbritter Minoru Takasato Mario R Guarracino Anestis Tsakiridis Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor eLife axial identity brachyury Hox neuromesodermal progenitors neural crest embryonic stem cells |
| 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 | axial identity brachyury Hox neuromesodermal progenitors neural crest embryonic stem cells |
| url | https://elifesciences.org/articles/74263 |
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