| Autor: |
Ilaria Granata, Ichcha Manipur, Thomas J. R. Frith, Matthew Wind, Mario Rosario Guarracino, Alessandro Bertero, Antigoni Gogolou, Florian Halbritter, Anestis Tsakiridis, Maria Guarini, Filip J. Wymeersch, Celine Souilhol, Minoru Takasato, Christoph Bock |
| Rok vydání: |
2021 |
| Předmět: |
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| Popis: |
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 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. In contrast, posteriorisation of NMP-derived spinal cord cells is TBXT/WNT-independent and takes place under the influence of 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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