Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor

  1. Antigoni Gogolou
  2. Celine Souilhol
  3. Ilaria Granata
  4. Filip J Wymeersch
  5. Ichcha Manipur
  6. Matthew Wind
  7. Thomas JR Frith
  8. Maria Guarini
  9. Alessandro Bertero
  10. Christoph Bock
  11. Florian Halbritter
  12. Minoru Takasato
  13. Mario R Guarracino
  14. Anestis Tsakiridis  Is a corresponding author
  1. University of Sheffield, United Kingdom
  2. National Research Council, Italy
  3. RIKEN Center for Biosystems Dynamics Research, Japan
  4. Austrian Academy of Sciences, Austria
  5. University of Torino, Italy
  6. St. Anna Children's Cancer Research Institute, Austria
  7. 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

The following data sets were generated

Article and author information

Author details

  1. Antigoni Gogolou

    Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Celine Souilhol

    Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Ilaria Granata

    Computational and Data Science Laboratory, National Research Council, Napoli, Italy
    Competing interests
    The authors declare that no competing interests exist.
  4. Filip J Wymeersch

    Laboratory for Human Organogenesis, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8999-4555
  5. Ichcha Manipur

    Computational and Data Science Laboratory, National Research Council, Napoli, Italy
    Competing interests
    The authors declare that no competing interests exist.
  6. Matthew Wind

    Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Thomas JR Frith

    Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Maria Guarini

    CeMM Research Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  9. Alessandro Bertero

    Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy
    Competing interests
    The authors declare that no competing interests exist.
  10. Christoph Bock

    CeMM Research Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6091-3088
  11. Florian Halbritter

    Developmental Cancer Genomics, St. Anna Children's Cancer Research Institute, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  12. Minoru Takasato

    Laboratory for Human Organogenesis, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0458-7414
  13. Mario R Guarracino

    University of Cassino and Southern Lazio, Cassino, Italy
    Competing interests
    The authors declare that no competing interests exist.
  14. Anestis Tsakiridis

    Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom
    For correspondence
    a.tsakiridis@sheffield.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2184-2990

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.

Metrics

  • 2,499
    views
  • 428
    downloads
  • 8
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Antigoni Gogolou
  2. Celine Souilhol
  3. Ilaria Granata
  4. Filip J Wymeersch
  5. Ichcha Manipur
  6. Matthew Wind
  7. Thomas JR Frith
  8. Maria Guarini
  9. Alessandro Bertero
  10. Christoph Bock
  11. Florian Halbritter
  12. Minoru Takasato
  13. Mario R Guarracino
  14. Anestis Tsakiridis
(2022)
Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor
eLife 11:e74263.
https://doi.org/10.7554/eLife.74263

Share this article

https://doi.org/10.7554/eLife.74263

Further reading

    1. Developmental Biology
    Thomas A Bos, Elizaveta Polyakova ... Monique RM Jongbloed
    Research Article Updated

    Human autonomic neuronal cell models are emerging as tools for modeling diseases such as cardiac arrhythmias. In this systematic review, we compared 33 articles applying 14 different protocols to generate sympathetic neurons and 3 different procedures to produce parasympathetic neurons. All methods involved the differentiation of human pluripotent stem cells, and none employed permanent or reversible cell immortalization. Almost all protocols were reproduced in multiple pluripotent stem cell lines, and over half showed evidence of neural firing capacity. Common limitations in the field are a lack of three-dimensional models and models that include multiple cell types. Sympathetic neuron differentiation protocols largely mirrored embryonic development, with the notable absence of migration, axon extension, and target-specificity cues. Parasympathetic neuron differentiation protocols may be improved by including several embryonic cues promoting cell survival, cell maturation, or ion channel expression. Moreover, additional markers to define parasympathetic neurons in vitro may support the validity of these protocols. Nonetheless, four sympathetic neuron differentiation protocols and one parasympathetic neuron differentiation protocol reported more than two-thirds of cells expressing autonomic neuron markers. Altogether, these protocols promise to open new research avenues of human autonomic neuron development and disease modeling.

    1. Cell Biology
    2. Developmental Biology
    Sarah Y Coomson, Salil A Lachke
    Insight

    A study in mice reveals key interactions between proteins involved in fibroblast growth factor signaling and how they contribute to distinct stages of eye lens development.