TY - JOUR T1 - Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor JF - bioRxiv DO - 10.1101/2021.09.24.461516 SP - 2021.09.24.461516 AU - Antigoni Gogolou AU - Celine Souilhol AU - Ilaria Granata AU - Filip J Wymeersch AU - Ichcha Manipur AU - Matthew Wind AU - Thomas JR Frith AU - Maria Guarini AU - Alessandro Bertero AU - Christoph Bock AU - Florian Halbritter AU - Minoru Takasato AU - Mario R Guarracino AU - Anestis Tsakiridis Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/09/24/2021.09.24.461516.abstract N2 - 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.Competing Interest StatementThe authors have declared no competing interest. ER -