Edar Receptor
Ectodysplasins
Receptors, Ectodysplasin
Edar-Associated Death Domain Protein
Ectodermal Dysplasia
Hypohidrosis
Xedar Receptor
Edar/Eda interactions regulate enamel knot formation in tooth morphogenesis. (1/48)
tabby and downless mutant mice have apparently identical defects in teeth, hair and sweat glands. Recently, genes responsible for these spontaneous mutations have been identified. downless (Dl) encodes Edar, a novel member of the tumour necrosis factor (TNF) receptor family, containing the characteristic extracellular cysteine rich fold, a single transmembrane region and a death homology domain close to the C terminus. tabby (Ta) encodes ectodysplasin-A (Eda) a type II membrane protein of the TNF ligand family containing an internal collagen-like domain. As predicted by the similarity in adult mutant phenotype and the structure of the proteins, we demonstrate that Eda and Edar specifically interact in vitro. We have compared the expression pattern of Dl and Ta in mouse development, taking the tooth as our model system, and find that they are not expressed in adjacent cells as would have been expected. Teeth develop by a well recorded series of epithelial-mesenchymal interactions, similar to those in hair follicle and sweat gland development, the structures found to be defective in tabby and downless mice. We have analysed the downless mutant teeth in detail, and have traced the defect in cusp morphology back to initial defects in the structure of the tooth enamel knot at E13. Significantly, the defect is distinct from that of the tabby mutant. In the tabby mutant, there is a recognisable but small enamel knot, whereas in the downless mutant the knot is absent, but enamel knot cells are organised into a different shape, the enamel rope, showing altered expression of signalling factors (Shh, Fgf4, Bmp4 and Wnt10b). 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. 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. Changes in the structure of the enamel knot signalling centre in downless tooth germs provide functional data directly linking the enamel knot with tooth cusp morphogenesis. We also show that the Lef1 pathway, thought to be involved in these mutants, functions independently in a parallel pathway. (+info)The medaka rs-3 locus required for scale development encodes ectodysplasin-A receptor. (2/48)
The bodies of most teleost fish species are covered with specialized subepithelial structures known as scales. The scale is an epithelial appendage that differentiates from the dermal mesenchyme. Mammals, on the other hand, have no scales, but instead their bodies are covered with hair. Although their appearances are quite different, scales and hair can be considered structurally similar in that both of them are epithelial appendages distributed over the body surface in an orderly pattern. This analogy suggests that they may have the same evolutionary origin. But, to date, no molecular evidence has been presented that links scales and hair. A mutation at the rs-3 locus of medaka (Oryzias latipes) leads to almost complete loss of scales. We demonstrated that the rs-3 locus encodes ectodysplasin-A receptor (EDAR), which is required for the initiation of hair development in mammals. We identified a novel transposon inserted in the first intron of EDAR, which causes aberrant splicing. This work shows that EDAR is required for scale development in fish and suggests that it is an evolutionarily conserved molecule that is required for the development of epithelial appendages in vertebrates. (+info)Fish scale development: Hair today, teeth and scales yesterday? (3/48)
A group of genes in the tumour necrosis factor signalling pathway are mutated in humans and mice with ectodermal dysplasias--a failure of hair and tooth development. A mutation has now been identified in one of these genes, ectodysplasin-A receptor, in the teleost fish Medaka, that results in a failure of scale formation. (+info)Requirement of NF-kappaB/Rel for the development of hair follicles and other epidermal appendices. (4/48)
NF-kappaB/Rel transcription factors and IkappaB kinases (IKK) are essential for inflammation and immune responses, but also for bone-morphogenesis, skin proliferation and differentiation. Determining their other functions has previously been impossible, owing to embryonic lethality of NF-kappaB/Rel or IKK-deficient animals. Using a gene targeting approach we have ubiquitously expressed an NF-kappaB super-repressor to investigate NF-kappaB functions in the adult. Mice with suppressed NF-kappaB revealed defective early morphogenesis of hair follicles, exocrine glands and teeth, identical to Eda (tabby) and Edar (downless) mutant mice. These affected epithelial appendices normally display high NF-kappaB activity, suppression of which resulted in increased apoptosis, indicating that NF-kappaB acts as a survival factor downstream of the tumor necrosis factor receptor family member EDAR. Furthermore, NF-kappaB is required for peripheral lymph node formation and macrophage function. (+info)Identification of a novel death domain-containing adaptor molecule for ectodysplasin-A receptor that is mutated in crinkled mice. (5/48)
Hypohydrotic Ectodermal Dysplasia (HED) is a genetic disease seen in humans and mice. It is characterized by loss of hair, sweat glands, and teeth. The predominant X-linked form results from mutations in ectodysplasin-A (EDA), a TNF-like ligand. A phenotypically indistinguishable autosomal form of the disease results from mutations in the receptor for EDA (EDAR). EDAR is a NF-kappaB-activating, death domain-containing member of the TNF receptor family. crinkled, a distinct autosomal form of HED, was discovered in a mouse strain in which both the ligand (EDA) and receptor (EDAR) were wild-type, suggestive of a disruption further downstream in the signaling pathway. Employing a forward genetic approach, we have cloned crinkled (CR) and find it to encode a novel death domain-containing adaptor. crinkled binds EDAR through a homotypic death domain interaction and mediates engagement of the NF-kappaB pathway, possibly by recruiting TRAF2 to the receptor-signaling complex. This is an unprecedented example of naturally occurring mutations in ligand, receptor, or adaptor giving rise to the same phenotypic disease characterized by a defect in the proper development of epidermal appendages. (+info)Regulation of hair follicle development by the TNF signal ectodysplasin and its receptor Edar. (6/48)
X-linked and autosomal forms of anhidrotic ectodermal dysplasia syndromes (HED) are characterized by deficient development of several ectodermal organs, including hair, teeth and exocrine glands. The recent cloning of the genes that underlie these syndromes, ectodysplasin (ED1) and the ectodysplasin A receptor (EDAR), and their identification as a novel TNF ligand-receptor pair suggested a role for TNF signaling in embryonic morphogenesis. In the mouse, the genes of the spontaneous mutations Tabby (Ta) and downless (dl) were identified as homologs of ED1 and EDAR, respectively. To gain insight into the function of this signaling pathway in development of skin and hair follicles, we analyzed the expression and regulation of Eda and Edar in wild type as well as Tabby and Lef1 mutant mouse embryos. 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. By using skin explant cultures, we further show that this signaling pathway is intimately associated with interactions between the epithelial and mesenchymal tissues. We also find that Ta mutants lack completely the placodes of the first developing tylotrich hairs, and that they do not show patterned expression of placodal genes, including Bmp4, Lef1, Shh, Ptch and Edar, and the genes for beta-catenin and activin A. Finally, we identified activin as a mesenchymal signal that stimulates Edar expression and WNT as a signal that induces Eda expression, suggesting a hierarchy of distinct signaling pathways in the development of skin and hair follicles. In conclusion, we suggest that Eda and Edar are associated with the onset of ectodermal patterning and that ectodysplasin/edar signaling also regulates the morphogenesis of hair follicles. (+info)WNT signals are required for the initiation of hair follicle development. (7/48)
Hair follicle morphogenesis is initiated by a dermal signal that induces the development of placodes in the overlying epithelium. To determine whether WNT signals are required for initiation of follicular development, we ectopically expressed Dickkopf 1, a potent diffusible inhibitor of WNT action, in the skin of transgenic mice. This produced a complete failure of placode formation prior to morphological or molecular signs of differentiation, and blocked tooth and mammary gland development before the bud stage. This phenotype indicates that activation of WNT signaling in the skin precedes, and is required for, localized expression of regulatory genes and initiation of hair follicle placode formation. (+info)Mucosal addressin cell adhesion molecule 1 plays an unexpected role in the development of mouse guard hair. (8/48)
The first wave of coat hair development is initiated around embryonic day 14 in the mouse. Whereas ectodysplasin and ectodermal dysplasia receptor, tumor necrosis factor and tumor necrosis factor receptor family molecules, respectively, were identified to be signals triggering this process, not much was known regarding their downstream molecular targets. In this report, we show that mucosal addressin cell adhesion molecule 1 and intercellular adhesion molecule 1 are induced in the keratinocytes of the hair placode as a direct consequence of ectodermal dysplasia receptor signal, and tumor-necrosis-factor-receptor-associated factor 6 is involved in this mucosal addressin cell adhesion molecule 1 expression. 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. Follicle development in this culture was also suppressed to some extent, though not completely, by addition of soluble mucosal addressin cell adhesion molecule 1/IgG-Fc chimeric protein, whereas monoclonal antibody that can inhibit mucosal addressin cell adhesion molecule 1 interaction with integrin alpha4beta7 had no effect on this process. 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. (+info)The EDA receptor (Ectodysplasin A receptor) is a gene that encodes a transmembrane protein involved in the development and maintenance of various tissues, including the skin and hair follicles. The Edar receptor plays a crucial role in the signaling pathway that regulates the formation and patterning of these structures during embryonic development. Mutations in this gene have been associated with several human genetic disorders, such as ectodermal dysplasia, which is characterized by abnormalities in the hair, teeth, nails, and sweat glands.
Ectodysplasins are a group of signaling proteins that play crucial roles in the development and differentiation of ectodermal tissues, including the skin, hair, nails, teeth, and sweat glands. They are involved in various signaling pathways and help regulate cell growth, migration, and pattern formation during embryogenesis. Mutations in genes encoding ectodysplasins can lead to genetic disorders characterized by abnormalities in these tissues, such as ectodermal dysplasia syndromes.
Ectodysplasin receptors are a group of proteins that belong to the tumor necrosis factor (TNF) receptor superfamily. They play crucial roles in the development and function of ectodermal tissues, which include the skin, hair, nails, teeth, and sweat glands.
There are two main types of Ectodysplasin receptors: EDAR (Ectodysplasin A Receptor) and XEDAR (X-linked Ectodysplasin A Receptor). These receptors bind to their respective ligands, Ectodysplasin A (EDA) and Ectodysplasin A2 (EDA2), which are also members of the TNF family.
When EDA or EDA2 binds to EDAR or XEDAR, it activates a signaling pathway that involves several downstream molecules, including TRAF6 (TNF Receptor-Associated Factor 6) and NF-κB (Nuclear Factor kappa-light-chain-enhancer of activated B cells). This signaling cascade ultimately leads to the regulation of gene expression and cellular responses that are essential for ectodermal development.
Mutations in the genes encoding EDA, EDAR, or XEDAR have been associated with various genetic disorders, such as ectodermal dysplasias, which are characterized by abnormalities in the development of ectodermal tissues.
Edar-associated death domain protein (EDARADD) is a gene that encodes for a protein involved in the signaling pathway of the ectodysplasin A receptor (EDAR). The EDAR signaling pathway plays crucial roles in the development of various organs, including skin, hair, teeth, and sweat glands.
The EDARADD protein contains a death domain that interacts with the death domain of EDAR upon activation by ectodysplasin A (EDA). This interaction leads to the recruitment of additional signaling proteins and ultimately activates downstream targets, which regulate cellular processes such as proliferation, differentiation, and apoptosis.
Mutations in the EDARADD gene have been associated with several human genetic disorders, including ectodermal dysplasias, hypohidrotic ectodermal dysplasia (HED), and an autosomal recessive form of cleft lip/palate. These conditions are characterized by abnormalities in the development of structures derived from the ectoderm, such as skin, hair, teeth, nails, and sweat glands.
Ectodermal dysplasia (ED) is a group of genetic disorders that affect the development and formation of ectodermal tissues, which include the skin, hair, nails, teeth, and sweat glands. The condition is usually present at birth or appears in early infancy.
The symptoms of ED can vary widely depending on the specific type and severity of the disorder. Common features may include:
* Sparse or absent hair
* Thin, wrinkled, or rough skin
* Abnormal or missing teeth
* Nail abnormalities
* Absent or reduced sweat glands, leading to heat intolerance and problems regulating body temperature
* Ear abnormalities, which can result in hearing loss
* Eye abnormalities
ED is caused by mutations in genes that are involved in the development of ectodermal tissues. Most cases of ED are inherited in an autosomal dominant or autosomal recessive pattern, meaning that a child can inherit the disorder even if only one parent (dominant) or both parents (recessive) carry the mutated gene.
There is no cure for ED, but treatment is focused on managing the symptoms and improving quality of life. This may include measures to maintain body temperature, such as cooling vests or frequent cool baths; dental treatments to replace missing teeth; hearing aids for hearing loss; and skin care regimens to prevent dryness and irritation.
Hypohidrosis is a medical condition characterized by reduced or absent sweating. It's the opposite of hyperhidrosis, which is excessive sweating. Sweating is an essential function that helps regulate body temperature through the evaporation of sweat on the skin surface. When this process is impaired due to hypohidrosis, it can lead to difficulties in maintaining a normal body temperature, especially during physical exertion or in hot environments.
Hypohidrosis may be localized, affecting only certain areas of the body, or generalized, affecting the entire body. The causes of hypohidrosis are varied and include genetic factors, nerve damage, skin disorders, dehydration, burns, or the use of certain medications. Depending on its underlying cause, hypohidrosis can be managed through appropriate treatments, such as addressing nerve damage, managing skin conditions, or adjusting medication usage.
I'm sorry for any confusion, but "Xedar Receptor" is not a recognized term in physiology or pharmacology. It seems like there might be a spelling error or typo in the receptor name you are looking for. Xedar is not a known drug or receptor.
If you meant "Xadagno/Dopamine Receptor," I can provide information on that. Xadago (generic name: safinamide) is a medication used to treat Parkinson's disease, and it acts as a dopamine reuptake inhibitor and a non-selective MAO-B inhibitor. The drug's primary mechanism of action involves increasing the concentration of dopamine in the brain by preventing its reuptake into presynaptic neurons and blocking monoamine oxidase B, which is responsible for breaking down dopamine.
If you had a different term or concept in mind, please provide clarification, and I will be happy to help further.
A tooth is a hard, calcified structure found in the jaws (upper and lower) of many vertebrates and used for biting and chewing food. In humans, a typical tooth has a crown, one or more roots, and three layers: the enamel (the outermost layer, hardest substance in the body), the dentin (the layer beneath the enamel), and the pulp (the innermost layer, containing nerves and blood vessels). Teeth are essential for proper nutrition, speech, and aesthetics. There are different types of teeth, including incisors, canines, premolars, and molars, each designed for specific functions in the mouth.