Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor
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 the childhood tumour neuroblastoma, are derived from neuromesodermal-potent progenitors of the postcranial body (NMPs). Here we employ human embryonic stem cell differentiation to define how 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.
Data availability
Sequencing data have been deposited in GEO under accession codes GSE184622, GSE184620 and GSE184227
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Early anteroposterior regionalization of human neural crest is shaped by a pro-mesodermal factorNCBI Gene Expression Omnibus, GSE184227.
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Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factorNCBI Gene Expression Omnibus, GSE184622.
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RNA sequencing of control and TBXT-depleted human NMP-like axial progenitorsNCBI Gene Expression Omnibus, GSE184620.
Article and author information
Author details
Funding
Biotechnology and Biological Sciences Research Council (BB/P000444/1)
- Anestis Tsakiridis
Horizon 2020 Framework Programme (824070)
- Anestis Tsakiridis
Medical Research Council (MR/V002163/1)
- Anestis Tsakiridis
Children's Cancer and Leukaemia Group (CCLGA 2019 28)
- Anestis Tsakiridis
Japan Society for the Promotion of Science (JP19K16157)
- Filip J Wymeersch
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Marianne E Bronner, California Institute of Technology, United States
Ethics
Animal experimentation: All animal experiments were approved by the Institutional Animal Experiments Committee of RIKEN Kobe Branch (A2016-03-10). Mice were handled in accordance with the ethics guidelines of the institute.
Version history
- Preprint posted: September 24, 2021 (view preprint)
- Received: September 27, 2021
- Accepted: September 25, 2022
- Accepted Manuscript published: September 26, 2022 (version 1)
- Version of Record published: October 6, 2022 (version 2)
Copyright
© 2022, Gogolou et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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