The transcription factor Sox9 is required for cranial neural crest development in Xenopus
Abstract
The SOX family of transcription factors has been implicated in cell fate specification during embryogenesis. One member of this family, Sox9, has been shown to regulate both chondrogenesis and sex determination in the mouse embryo. Heterozygous mutations in Sox9 result in Campomelic Dysplasia (CD), a lethal human disorder characterized by autosomal XY sex reversal, severe skeletal malformations and several craniofacial defects. Sox9 is also expressed in neural crest progenitors but very little is known about the function of Sox9 in the neural crest. We have cloned the Xenopus homolog of the Sox9 gene. It is expressed maternally and accumulates shortly after gastrulation at the lateral edges of the neural plate, in the neural crest-forming region. As development proceeds, Sox9 expression persists in migrating cranial crest cells as they populate the pharyngeal arches. Depletion of Sox9 protein in developing embryos, using morpholino antisense oligos, causes a dramatic loss of neural crest progenitors and an expansion of the neural plate. Later during embryogenesis, morpholino-treated embryos have a specific loss or reduction of neural crest-derived skeletal elements, mimicking one aspect of the craniofacial defects observed in CD patients. We propose that Sox9 is an essential component of the regulatory pathway that leads to cranial neural crest formation.
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A manually curated signature from an extensive literature review validated the cranial identity of the NCSC lines, and clustering by Pearson correlation excluded genotype- or hairpin-specific expression changes.
“As shown in fig. S2A, a manually curated signature from an extensive literature review (23–28) validated the cranial identity of our NCSC lines, while clustering by Pearson correlation excluded the presence of any genotype- or hairpin-specific expression change.”
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- Authors
- Spokony, R. F., Aoki, Y., Saint-Germain, N., Magner-Fink, E., & Saint-Jeannet, J.-P.
- Affiliations
- University of Pennsylvania (US)
- These authors contributed equally to this work
- Corresponding author
- Aoki, Yoichiro
- ORCID
- Spokony, Rebecca F.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2002-01-15
- Volume
- 129
- Issue
- 2
- Pages
- 421-432
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2103780536
- Cited by
- 295
- References
- 85
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 12 · 2023: 11 · 2022: 12 · 2021: 13 · 2020: 5 · 2019: 10 · 2018: 10 · 2017: 8 · 2016: 10 · 2015: 9 · 2014: 4 · 2013: 8 · 2012: 16
- FWCI
- 7.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Development (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Craniofacial Disorders and Treatments
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- SOX9, cranial neural crest, neural crest development, Sox transcription factors, campomelic dysplasia, neural crest progenitors, neural plate, branchial arches, craniofacial defects, skeletal deformities, sex determination, Xenopus embryo, morpholino knockdown
- MeSH terms
- Snail Family Transcription Factors, Amino Acid Sequence, Animals, Embryo, Nonmammalian, High Mobility Group Proteins, Humans, Microinjections, Molecular Sequence Data, Morphogenesis, Morpholines, Neural Crest, RNA, Messenger, Sex Differentiation, Transcription Factors, Xenopus laevis, Biomarkers, Sequence Alignment, In Situ Hybridization, Gene Expression Regulation, Developmental, Craniofacial Abnormalities, Oligodeoxyribonucleotides, Antisense, Xenopus Proteins, Embryonic Development, SOX9 Transcription Factor
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