Enhanced ectodysplasin-A receptor (EDAR) signaling alters multiple fiber characteristics to produce the East Asian hair form
Open accessAbstract
Hair morphology differs dramatically between human populations: people of East Asian ancestry typically have a coarse hair texture, with individual fibers being straight, of large diameter, and cylindrical when compared to hair of European or African origin. Ectodysplasin-A receptor (EDAR) is a cell surface receptor of the tumor necrosis factor receptor (TNFR) family involved in the development of hair follicles, teeth, and sweat glands. Analyses of genome-wide polymorphism data from multiple human populations suggest that EDAR experienced strong positive selection in East Asians. It is likely that a nonsynonymous SNP in EDAR, rs3827760, was the direct target of selection as the derived p.Val370Ala variant is seen at high frequencies in populations of East Asian and Native American origin but is essentially absent from European and African populations. Here we demonstrate that the derived EDAR370A common in East Asia has a more potent signaling output than the ancestral EDAR370 V in vitro. We show that elevation of Edar activity in transgenic mice converts their hair phenotype to the typical East Asian morphology. The coat texture becomes coarse, with straightening and thickening of individual hairs and conversion of fiber cross-sectional profile to a circular form. These thick hair fibers are produced by enlarged hair follicles, which in turn develop from enlarged embryonic organ primordia. This work shows that the multiple differences in hair form between East Asian and other human populations can be explained by the simplest of genetic alterations.
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Recent work has identified this allele of EDAR as having an enhanced effect on Eda signaling in mouse models containing the altered human residue.
“It is interesting to note that recent work has identified this allele of EDAR as having an enhanced effect on Eda signaling in mouse models containing the altered human residue [59].”
From Zebrafish eda and edar Mutants Reveal Conserved and Ancestral Roles of Ectodysplasin Signaling in Vertebrates (2008) · cites this paper as [59]
The indexed title states that EDAR signaling is enhanced, and the metadata lists transgenic mice and an amino-acid substitution. However, the available passages do not establish that mouse models containing the altered human residue showed enhanced Eda signaling. (LLM, conf=0.72)
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Cites
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- Authors
- Mou, C., Thomason, H. A., Willan, P. M., Clowes, C., Harris, W. E., Drew, C. F., Dixon, J., Dixon, M. J., & Headon, D. J.
- Affiliations
- University of Manchester (GB)
- Corresponding author
- Headon, Denis J.
- Venue
- Human Mutation
- Publisher
- Hindawi Limited
- Published
- 2008-12
- Volume
- 29
- Issue
- 12
- Pages
- 1405-1411
- ISSN
- 1059-7794 (ISSN-L)
- 1098-1004
- OpenAlex
- W2016547423
- Cited by
- 106
- References
- 2
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 6 · 2021: 11 · 2020: 6 · 2019: 9 · 2018: 7 · 2017: 5 · 2016: 9 · 2015: 3 · 2014: 9 · 2013: 9 · 2012: 4
- FWCI
- 6.50
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Human Mutation (publishedVersion)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Research Explorer (The University of Manchester) (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › dental development and anomalies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Keywords
- EDAR, hair morphology, hair follicle development, positive selection, TNF receptor signaling, transgenic mice, human population variation
- MeSH terms
- Amino Acid Sequence, Animals, Cell Line, Hair, Humans, Mice, Transgenic, Sequence Alignment, Amino Acid Substitution, Polymorphism, Single Nucleotide, Asian People, Mice, Edar Receptor
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