title: Ectodysplasin A (EDA) - EDA receptor signalling and its pharmacological modulation.
abstract: The TNF family ligand ectodysplasin A (EDA) regulates the induction, morphogenesis and/or maintenance of skin-derived structures such as teeth, hair, sweat glands and several other glands. Deficiencies in the EDA - EDA receptor (EDAR) signalling pathway cause hypohidrotic ectodermal dysplasia (HED). This syndrome is characterized by the absence or malformation of several skin-derived appendages resulting in hypotrychosis, hypodontia, heat-intolerance, dry skin and dry eyes, susceptibility to airways infections and crusting of various secretions. The EDA-EDAR system is an important effector of canonical Wnt signalling in developing skin appendages. It functions by stimulating NF-κB-mediated transcription of effectors or inhibitors of the Wnt, Sonic hedgehog (SHH), fibroblast growth factor (FGF) and transforming growth factor beta (TGFβ) pathways that regulate interactions within or between epithelial and mesenchymal cells and tissues. In animal models of Eda-deficiency, soluble EDAR agonists can precisely correct clinically relevant symptoms with low side effects even at high agonist doses, indicating that efficient negative feedback signals occur in treated tissues. Hijacking of the placental antibody transport system can help deliver active molecules to developing foetuses in a timely manner. EDAR agonists may serve to treat certain forms of ectodermal dysplasia.
authors: Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland.
authors: Christine
authors: C
authors: Kowalczyk-Quintas
authors: Department of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland. Electronic address: pascal.schneider@unil.ch.
authors: Pascal
authors: P
authors: Schneider
mesh_terms: D000818:Animals; D004285:Dogs; D053358:Ectodermal Dysplasia 1, Anhidrotic / Q000188:drug therapy / Q000235:genetics*; D053331:Ectodysplasins / Q000235:genetics*; D053339:Edar Receptor / Q000819:agonists / Q000235:genetics*; D004847:Epithelial Cells / Q000166:cytology; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D009024:Morphogenesis; D016328:NF-kappa B / Q000235:genetics; D012867:Skin / Q000254:growth & development*; D012879:Skin Physiological Phenomena / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D051153:Wnt Proteins / Q000037:antagonists & inhibitors; D060449:Wnt Signaling Pathway
chemical_list: C506018:EDA protein, human; C506008:EDAR protein, human; D053331:Ectodysplasins; D053339:Edar Receptor; D053823:Hedgehog Proteins; D016328:NF-kappa B; C509239:SHH protein, human; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D005346:Fibroblast Growth Factors
keywords: Ectodermal dysplasia; Ectodysplasin; Hair; TNF family; Tooth