The ectodysplasin pathway: from diseases to adaptations.
The ectodysplasin (EDA) pathway, which is active during the development of ectodermal organs, including teeth, hairs, feathers, and mammary glands, and which is crucial for fine-tuning the developmental network controlling the number, size, and density of these structures, was discovered by studying human patients affected by anhidrotic/hypohidrotic ectodermal dysplasia. It comprises three main gene products: EDA, a ligand that belongs to the tumor necrosis factor (TNF)-α family, EDAR, a receptor related to the TNFα receptors, and EDARADD, a specific adaptor. This core pathway relies on downstream NF-κB pathway activation to regulate target genes. The pathway has recently been found to be associated with specific adaptations in natural populations: the magnitude of armor plates in sticklebacks and the hair structure in Asian human populations. Thus, despite its role in human disease, the EDA pathway is a 'hopeful pathway' that could allow adaptive changes in ectodermal appendages which, as specialized interfaces with the environment, are considered hot-spots of morphological evolution.
Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique (CNRS), Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69364 Lyon CEDEX 07, France.
Alexa
A
Sadier
Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique (CNRS), Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69364 Lyon CEDEX 07, France.
Laurent
L
Viriot
Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique (CNRS), Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69364 Lyon CEDEX 07, France.
Sophie
S
Pantalacci
Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique (CNRS), Ecole Normale Supérieure de Lyon, 46 allée d'Italie, 69364 Lyon CEDEX 07, France. Electronic address: Vincent.Laudet@ens-lyon.fr.
Vincent
V
Laudet
D000222:Adaptation, Physiological / Q000235:genetics*; D000818:Animals; D053358:Ectodermal Dysplasia 1, Anhidrotic / Q000235:genetics*; D053331:Ectodysplasins / Q000235:genetics* / Q000378:metabolism; D053339:Edar Receptor / Q000235:genetics / Q000378:metabolism; D053362:Edar-Associated Death Domain Protein / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014714:Vertebrates / Q000235:genetics
D053331:Ectodysplasins; D053339:Edar Receptor; D053362:Edar-Associated Death Domain Protein; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor
adaptation; anhidrotic/hypohidrotic ectodermal dysplasia; ectodermal appendages; ectodysplasin; signaling pathways