Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor
- University of Sheffield, United Kingdom
- National Research Council, Italy
- RIKEN Center for Biosystems Dynamics Research, Japan
- Austrian Academy of Sciences, Austria
- University of Torino, Italy
- St. Anna Children's Cancer Research Institute, Austria
- University of Cassino and Southern Lazio, Italy
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
Anestis Tsakiridis
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.
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.
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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Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor
eLife 11:e74263.
https://doi.org/10.7554/eLife.74263
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