Genetic ablation of neural crest cell diversification
Open accessAbstract
The neural crest generates multiple cell types during embryogenesis but the mechanisms regulating neural crest cell diversification are incompletely understood. Previous studies using mutant zebrafish indicated that foxd3 and tfap2a function early and differentially in the development of neural crest sublineages. Here, we show that the simultaneous loss of foxd3 and tfap2a function in zebrafish foxd3zdf10;tfap2alow double mutant embryos globally prevents the specification of developmentally distinct neural crest sublineages. By contrast, neural crest induction occurs independently of foxd3 and tfap2a function. We show that the failure of neural crest cell diversification in double mutants is accompanied by the absence of neural crest sox10 and sox9a/b gene expression,and that forced expression of sox10 and sox9a/bdifferentially rescues neural crest sublineage specification and derivative differentiation. These results demonstrate the functional necessity for foxd3 and tfap2a for neural crest sublineage specification and that this requirement is mediated by the synergistic regulation of the expression of SoxE family genes. Our results identify a genetic regulatory pathway functionally discrete from the process of neural crest induction that is required for the initiation of neural crest cell diversification during embryonic development.
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NC-specific expression of sox9a, sox9b and sox10 depends on both foxd3 and tfap2a function in zebrafish embryos.
“NC-specific expression of sox9a, sox9b and sox10 has been shown to depend on both foxd3 and tfap2a function in zebrafish embryos [49].”
From A systems biology approach uncovers the core gene regulatory network governing iridophore fate choice from the neural crest (2018) · cites this paper as [49]
Our data support the above finding, showing that transcriptional regulation of tfec via Tfap2 transcription factors is independent of them first activating sox10 or sox9b.
“Our data support the above finding, showing that transcriptional regulation of tfec via Tfap2 transcription factors is independent of them first activating sox10 or sox9b [49–51] (Fig 9B).”
From The MITF paralog tfec is required in neural crest development for fate specification of the iridophore lineage from a multipotent pigment cell progenitor (2021) · cites this paper as [49]
The Results and Discussion describe tfap2a and foxd3 regulation of sox10 and sox9b in neural crest cells. A search for tfec in our full-text copy found no passage addressing its regulation or whether that regulation is independent of prior sox10 or sox9b activation. (LLM, conf=0.75)
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- Bi, W., Huang, W., Whitworth, D. J., Deng, J. M., Zhang, Z., Behringer, R. R. and de Crombrugghe, B. (2001). Haploinsufficiency of Sox9 results in defective cartilage primordial and premature skeletal mineralization. Proc. Natl. Acad. Sci. USA 98, 6698-6703.
- Herbarth, B., Pingault, V., Bondurand, N., Kuhlbrodt, K., Hermans- Borgmeyer, I., Puliti, A., Lemort, N., Goosens, M. and Wegner, M. (1998). Mutation of the Syr-related Sox10 gene in Dominant megacolon, a mouse model for human Hirschprung disease. Proc. Natl. Acad. Sci. USA 95, 5161- 5165.
- LeDouarin, N. and Kalcheim, C. (1999). The Neural Crest. New York: Cambridge University Press.
- Mori-Akiyama, Y., Akiyama, H., Rowitch, D. H. and de Crombrugghe, B. (2003). Sox9 is required for determination of the chondrogenic cell lineage in the cranial neural crest. Proc. Natl. Acad. Sci. USA 100, 9360-9365.
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- Authors
- Arduini, B. L., Bosse, K. M., & Henion, P. D.
- Affiliations
- The Ohio State University (US)
- Corresponding author
- Henion, Paul D.
- ORCID
- Arduini, Brigitte L.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2009-06-15
- Volume
- 136
- Issue
- 12
- Pages
- 1987-1994
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- PMC
- PMC2685722
- OpenAlex
- W2118160713
- Cited by
- 66
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 1 · 2021: 6 · 2020: 1 · 2019: 9 · 2018: 2 · 2017: 4 · 2016: 3 · 2015: 5 · 2014: 4 · 2013: 4 · 2012: 10
- FWCI
- 2.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (NS045758)
- National Institute of General Medical Sciences (R01GM076505, GM076505)
- National Institute of Neurological Disorders and Stroke (P30NS045758)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Keywords
- neural crest, FOXD3, TFAP2A, SOX10, neural crest induction, zebrafish, double mutants, rescue
- MeSH terms
- Animals, Embryo, Nonmammalian, Mutation, Neural Crest, Zebrafish, Gene Expression Regulation, Developmental, Cell Lineage, Zebrafish Proteins, Transcription Factor AP-2, Forkhead Transcription Factors, SOX9 Transcription Factor
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