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...

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Bibliographic Details
Published in:eLife 2022-09, Vol.11
Main Authors: Gogolou, Antigoni, Souilhol, Celine, Granata, Ilaria, Wymeersch, Filip J, Manipur, Ichcha, Wind, Matthew, Frith, Thomas JR, Guarini, Maria, Bertero, Alessandro, Bock, Christoph, Halbritter, Florian, Takasato, Minoru, Guarracino, Mario R, Tsakiridis, Anestis
Format: Article
Language:English
Subjects:
axial identity
brachyury
Cell differentiation
Children
Chromatin
Chromatin remodeling
Developmental Biology
Embryonic stem cells
Embryos
Enhancers
Fibroblast growth factors
Gene clusters
Gene expression
Hox
HOX gene
Neural crest
Neural stem cells
Neuroblastoma
neuromesodermal progenitors
Pharmaceutical industry
Progenitor cells
Scientific equipment and supplies industry
Spinal cord
Stem Cells and Regenerative Medicine
Tetracycline
Tetracyclines
Tumors
Wnt protein
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Summary: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.74263