From pioneer to repressor: Bimodal foxd3 activity dynamically remodels neural crest regulatory landscape in vivo
Open accessPreprint — published as 10.1016/j.devcel.2018.11.009 · Paper page
Abstract
The neural crest (NC) is a transient embryonic stem cell population characterised by its multipotency and broad developmental potential. Here, we perform NC-specific transcriptional and epigenomic profiling of foxd3 -mutant versus wild type cells in vivo to define the gene regulatory circuits controlling NC specification. Together with global binding analysis obtained by foxd3 biotin-ChIP and single cell profiles of foxd3 -expressing premigratory NC, our analysis shows that during early steps of NC formation, foxd3 acts globally as a pioneer factor to prime the onset of genes regulating NC specification and migration by re-arranging the chromatin landscape, opening cis -regulatory elements and reshuffing nucleosomes. Strikingly, foxd3 then switches from an activator to its canonical role as a transcriptional repressor. Taken together, these results demonstrate that foxd3 acts bimodally in the neural crest as a switch from permissive to repressive nucleosome/chromatin organisation to maintain stemness and define cell fates.
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A recent study suggests FoxD3 has a new role as a pioneer factor in neural crest development.
“a recent study suggests a new role for FoxD3, namely as a pioneer factor in neural crest development [56]”
From A systems biology approach uncovers the core gene regulatory network governing iridophore fate choice from the neural crest (2018) · cites this paper as [56]
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Research works printed but not linked: 2
- Betancur, P., Bronner-Fraser, M., and Sauka-Spengler, T. (2010b). Genomic code for Sox10 activation reveals a key regulatory enhancer for cranial neural crest. Proceedings of the National Academy of Sciences of the United States of America 107, 3570-3575.
- Westerfield, M. (2000). The zebrafish book. A guide for the laboratory use of zebrafish (Danio rerio), 4th edn (Univ. of Oregon Press).
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Petratou, K., Subkhankulova, T., Lister, J. A., Rocco, A., Schwetlick, H., & Kelsh, R. N. (2018) · PLOS Genetics · doi:10.1371/journal.pgen.1007402 · Cited by 69 · see citing works
Towards a gene regulatory network shaping the fins of the Princess cichlid
Ahi, E. P., & Sefc, K. M. (2018) · Scientific Reports · doi:10.1038/s41598-018-27977-y · Cited by 23 · see citing works
- Authors
- Gavriouchkina, D., Williams, R. M., Lukoseviciute, M., Hochgreb-Hägele, T., Senanayake, U., Chong-Morrison, V., Thongjuea, S., Repapi, E., Mead, A., & Sauka-Spengler, T.
- Affiliations
- University of Oxford (GB)
- ORCID
- Venue
- Developmental Cell
- Publisher
- openRxiv
- Published
- 2017-11-22
- Volume
- 47
- Issue
- 5
- Pages
- 608-628.e6
- ISSN
- 1534-5807 (ISSN-L)
- PMC
- PMC6286384
- OpenAlex
- W2772957859
- Cited by
- 116
- References
- 0
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 6 · 2023: 15 · 2022: 14 · 2021: 32 · 2020: 11 · 2019: 15 · 2018: 6
- FWCI
- 5.66
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Developmental Cell (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, other-oa)
- Research Explorer (The University of Manchester) (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- March of Dimes Foundation
- Leverhulme Trust (RPG-2015-026, RPG-2015)
- Lister Institute of Preventive Medicine
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Stavros Niarchos Foundation
- Medical Research Council (MR/M00919X/1, #G0902418)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Keywords
- FOXD3, neural crest, transcriptional repressor, pioneer factors, chromatin organization, nucleosome remodeling, cis-regulatory elements, neural crest specification, neural crest migration, transcriptional regulatory networks, epigenomics, gene expression profiling, cell fate determination, multipotency
- MeSH terms
- Animals, Enhancer Elements, Genetic, Neural Crest, Zebrafish, Gene Expression Regulation, Developmental, Zebrafish Proteins, Chromatin Assembly and Disassembly, Forkhead Transcription Factors
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