Gogolou, A orcid.org/0000-0002-3581-2426, Souilhol, C, Granata, I et al. (11 more authors) (2022) Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor. eLife, 11. ISSN 2050-084X
Abstract
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2022 Gogolou et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. (https://creativecommons.org/licenses/by/4.0/) |
Keywords: | Hox; axial identity; brachyury; developmental biology; embryonic stem cells; human; mouse; neural crest; neuromesodermal progenitors; regenerative medicine; stem cells; Cell Differentiation; Humans; Mesoderm; Neural Crest; Transcription Factors; Wnt Signaling Pathway |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Funding Information: | Funder Grant number BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL BB/P000444/1 EUROPEAN COMMISSION - HORIZON 2020 824070 MEDICAL RESEARCH COUNCIL MR/V002163/1 Children's Cancer and Leukaemia Group CCLGA 2019 28 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 01 Nov 2022 14:43 |
Last Modified: | 25 Sep 2024 13:15 |
Status: | Published |
Publisher: | eLife Sciences Publications Ltd |
Refereed: | Yes |
Identification Number: | 10.7554/elife.74263 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:192646 |