Disease relevance of Edar

• Mutations in Eda, Edar or other molecules of this signaling pathway cause ectodermal dysplasias characterized by defective development of teeth, hairs, and several exocrine glands such as sweat glands presumably due to impaired NF-kappaB response [1].

Psychiatry related information on Edar

• The stimulation of mouse locomotor activity caused by dl- and d-amphetamine in mice treated with adenine was less than that caused by equal dosage of these agents in mice not treated with adenine [2].

High impact information on Edar

• Mice with mutations in the downless (dl) gene have defects in hair follicle induction, lack sweat glands and have malformed teeth [3].
• The mutated locus has been physically mapped in this family, and a 200-kb mouse YAC clone, YAC D9, has been identified and shown to rescue the dl phenotype in the spontaneous dl(Jackson) (dl(J), recessive) and Dl(sleek) (Dl(slk), dominant negative) mutants [3].
• One branch of the family, dl(OVE1B), carries an approximately 600-kb deletion at the dl locus caused by transgene integration [3].
• Edar is a death domain protein of the TNFR family that is required for the development of hair, teeth and other ectodermal derivatives [4].
• The crux of this patterning mechanism is rapid Edar-positive feedback in the epidermis coupled with induction of dermal BMP4/7 [5].

Biological context of Edar

• Edar/Eda interactions regulate enamel knot formation in tooth morphogenesis [6].
• We could not, however, reproduce the downless phenotype, suggesting the existence of yet another ligand or receptor, or of ligand-independent activation mechanisms for Edar [6].
• Catagen development accompanied by increased apoptosis in the outer root sheath was significantly accelerated in downless mice or after treatment of wild-type mice by a fusion protein that inhibits Edar signaling, compared with the corresponding controls [7].
• Ectodysplasin, Edar and TNFRSF19 are expressed in complementary and overlapping patterns during mouse embryogenesis [8].
• 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 [9].

Anatomical context of Edar

• Regulation of hair follicle development by the TNF signal ectodysplasin and its receptor Edar [10].
• We show that Eda and Edar expression is confined to the ectoderm and occurs in a pattern that suggests a role of ectodysplasin/Edar signaling in the interactions between the ectodermal compartments and the formation and function of hair placodes [10].
• By adding a soluble form of Edar to tooth germs, we were able to mimic the tabby enamel knot phenotype, demonstrating the involvement of endogenous Eda in tooth development [6].
• tabby and downless mutant mice have apparently identical defects in teeth, hair and sweat glands [6].
• Thus, our 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 [7].

Associations of Edar with chemical compounds

• Ectodysplasin (Eda), a member of the tumor necrosis factor (TNF) superfamily, and its receptor Edar are necessary components of ectodermal organ development [8].
• THC most closely resembled DPH in the tests with chemical convulsant agents, but a sedative action of THC, resembling that of PB and CDP, was indicated by low ED5 0 for increased latency and for prevention of mortality in the MES test [11].

Regulatory relationships of Edar

• Experiments using an in vitro culture of skin fragments demonstrated that ectodermal-dysplasia-receptor-induced mucosal addressin cell adhesion molecule 1 expression occurs at the initial phase of follicle development before involvement of Sonic hedgehog signal [12].
• Ectodysplasin and Edar are expressed in separate epithelial compartments in the developing brain and the lacrimal gland [8].

Other interactions of Edar

• In downless and c(IkappaBalphaDeltaN) mice, placodes start to develop, but rapidly abort in the absence of EdaR/NF-kappaB signalling [13].
• These results demonstrated for the first time that the structural proteins, mucosal addressin cell adhesion molecule 1 and intercellular adhesion molecule 1, are induced by ectodermal dysplasia receptor signal and suggested the potential involvement of mucosal addressin cell adhesion molecule 1 in the morphogenesis of follicular keratinocytes [12].
• Of the three remaining mutants, one, with the suggested symbol Cat-5, mapped to the proximal region of Chromosome 10, 23.4 +/- 4.0 cM from downless (dl), a region with homology to human 6q [14].
• The expression pattern of Edar and Shh genes, and P-cadherin protein during the hair follicle development in the two types of transplants supported the above conclusion [15].
• We also studied the expression pattern of a related TNF receptor, TNFRSF19, and show that it is expressed in an overlapping domain with Edar in the tooth, mammary gland, whiskers, and limb bud suggesting a potentially redundant role [8].

Analytical, diagnostic and therapeutic context of Edar

• Our in situ hybridization analysis of the expression of ectodysplasin (encoded by the Tabby gene) and edar (encoded by the downless gene) during mouse tooth morphogenesis showed that they are expressed in complementary patterns exclusively in ectodermal tissue layer [16].
• To determine which of the YACs contain the dl gene, we generated YAC transgenic mice by mouse embryo microinjections [17].

References