Enhanced ectodysplasin‐A receptor (EDAR) signaling alters multiple fiber characteristics to produce the East Asian hair form

@article{Mou2008EnhancedER,
  title={Enhanced ectodysplasin‐A receptor (EDAR) signaling alters multiple fiber characteristics to produce the East Asian hair form},
  author={Chunyan Mou and Helen A. Thomason and Pamela M. Willan and Christopher Clowes and W. Edwin Harris and Caroline F. Drew and Jill Dixon and Michael J Dixon and Denis J. Headon},
  journal={Human Mutation},
  year={2008},
  volume={29}
}
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… 
A replication study confirmed the EDAR gene to be a major contributor to population differentiation regarding head hair thickness in Asia
TLDR
The results indicate that EDAR is the genetic determinant of hair thickness as well as a strong contributor to hair fiber thickness variation among Asian populations.
Characterisation of a second gain of function EDAR variant, encoding EDAR380R, in East Asia
TLDR
A second SNV with partly overlapping geographic distribution, the same in vitro functional effect and similar evolutionary age as the derived allele of rs3827760, but of independent origin and not exhibiting the same signs of strong selection, suggests a northern focus of positive selection on EDAR function in East Asia.
The adaptive variant EDARV370A is associated with straight hair in East Asians
TLDR
The results indicate very different biological mechanisms of straight hair in Europe and Asia, and present a more comprehensive picture of the phenotypic consequences of 370A, providing important clues into the potential adaptive forces shaping the evolution of this extraordinary genetic variant.
Enhanced Edar Signalling Has Pleiotropic Effects on Craniofacial and Cutaneous Glands
TLDR
Examination of changes in glandular structure caused by elevation of Edar signalling in a transgenic mouse model finds that sebaceous and Meibomian glands are enlarged and that salivary and mammary glands are more elaborately branched with increased Edar activity.
Recent positive selection of a human androgen receptor/ectodysplasin A2 receptor haplotype and its relationship to male pattern baldness
TLDR
The haplotype homozygosity suggests that the AGA risk haplotype was driven to high frequency by positive selection in Europeans although a low meiotic recombination rate contributed to the high haplotypehomozygosity.
Ectodysplasin A (EDA) - EDA receptor signalling and its pharmacological modulation.
Ectodysplasin research--where to next?
EDARV370A associated facial characteristics in Uyghur population revealing further pleiotropic effects
TLDR
Partial least square path model confirms EDARV370A systematically affect these weakly related ectodermal-derived characteristics, suggesting the pleiotropic effect of EDARv370A mainly plays roles in early embryo development.
...
...

References

SHOWING 1-10 OF 44 REFERENCES
A scan for genetic determinants of human hair morphology: EDAR is associated with Asian hair thickness.
TLDR
It is concluded that EDAR is a major genetic determinant of Asian hair thickness and the 1540C allele spread through Asian populations due to recent positive selection.
Ectodysplasin regulates pattern formation in the mammalian hair coat
TLDR
Evidence of follicular patterning by ectodysplasin A1 (Eda‐A1) is presented, a signaling protein necessary for the proper development of hair and other appendages, in transgenic mice, and shows that Eda-A1 can regulate basic developmental decisions, as cells were switched from interfollicular to follicular fates.
Ectodysplasin regulates the lymphotoxin-beta pathway for hair differentiation.
TLDR
Comparative transcription profiling of embryonic skin during hair follicle development in WT and Ta mice identified critical anhidrotic/hypohidrotic ectodermal dysplasia (EDA) effectors in four pathways, three already implicated in follicle formation.
Edar signaling in the control of hair follicle development.
TLDR
Genetic and experimental studies suggest that Edar signaling is involved in the control of cell fate decision in embryonic epidermis, as well as in the regulation of cell differentiation programs in the HF.
Involvement of the Edar signaling in the control of hair follicle involution (catagen).
TLDR
The data demonstrate that in addition to its well-established role in HF morphogenesis, Edar signaling is also involved in hair cycle control and regulates apoptosis in HF keratinocytes during catagen.
Ectodysplasin has a dual role in ectodermal organogenesis: inhibition of Bmp activity and induction of Shh expression
TLDR
Two signalling outcomes of the Eda pathway are reported: suppression of bone morphogenetic protein (Bmp) activity and upregulation of sonic hedgehog (Shh) signalling, indicating that suppression of Bmp activity was compromised in the absence of Eda.
Involvement of a novel Tnf receptor homologue in hair follicle induction
TLDR
The positional cloning of the dl gene is reported, which encodes a novel member of the tumour necrosis factor (Tnf) receptor ( Tnfr) family, and the mutant phenotype and dl expression pattern suggests that this gene encode a receptor that specifies hair follicle fate.
Death Receptor Signaling Giving Life to Ectodermal Organs
TLDR
Ectodysplasin-EDAR signaling mediates cell interactions within the ectoderm and regulates the initiation and morphogenesis of hair and teeth, indicating that this pathway and its function have been conserved during the evolution of ectodermal organs.
Permanent correction of an inherited ectodermal dysplasia with recombinant EDA
TLDR
This work shows that treatment of pregnant Tabby mice with a recombinant form of EDA1, engineered to cross the placental barrier, permanently rescues the Tabby phenotype in the offspring, the first example of a developmental genetic defect that can be permanently corrected by short-term treatment withA recombinant protein.
...
...