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
-
Early anteroposterior regionalization of human neural crest is shaped by a pro-mesodermal factorNCBI Gene Expression Omnibus, GSE184227.
-
Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factorNCBI Gene Expression Omnibus, GSE184622.
-
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.
Metrics
-
- 2,310
- views
-
- 411
- downloads
-
- 7
- 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)
Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor
eLife 11:e74263.
https://doi.org/10.7554/eLife.74263
Further reading
-
- Cell Biology
- Developmental Biology
In most murine species, spermatozoa exhibit a falciform apical hook at the head end. The function of the sperm hook is not yet clearly understood. In this study, we investigate the role of the sperm hook in the migration of spermatozoa through the female reproductive tract in Mus musculus (C57BL/6), using a deep tissue imaging custom-built two-photon microscope. Through live reproductive tract imaging, we found evidence indicating that the sperm hook aids in the attachment of spermatozoa to the epithelium and facilitates interactions between spermatozoa and the epithelium during migration in the uterus and oviduct. We also observed synchronized sperm beating, which resulted from the spontaneous unidirectional rearrangement of spermatozoa in the uterus. Based on live imaging of spermatozoa-epithelium interaction dynamics, we propose that the sperm hook plays a crucial role in successful migration through the female reproductive tract by providing anchor-like mechanical support and facilitating interactions between spermatozoa and the female reproductive tract in the house mouse.
-
- Developmental Biology
The morphogen FGF8 establishes graded positional cues imparting regional cellular responses via modulation of early target genes. The roles of FGF signaling and its effector genes remain poorly characterized in human experimental models mimicking early fetal telencephalic development. We used hiPSC-derived cerebral organoids as an in vitro platform to investigate the effect of FGF8 signaling on neural identity and differentiation. We found that FGF8 treatment increases cellular heterogeneity, leading to distinct telencephalic and mesencephalic-like domains that co-develop in multi-regional organoids. Within telencephalic regions, FGF8 affects the anteroposterior and dorsoventral identity of neural progenitors and the balance between GABAergic and glutamatergic neurons, thus impacting spontaneous neuronal network activity. Moreover, FGF8 efficiently modulates key regulators responsible for several human neurodevelopmental disorders. Overall, our results show that FGF8 signaling is directly involved in both regional patterning and cellular diversity in human cerebral organoids and in modulating genes associated with normal and pathological neural development.
