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Gene Review

Eda  -  ectodysplasin-A

Mus musculus

Synonyms: EDA protein homolog, EDA1, Ectodysplasin-A, Ed1, Eda-A1, ...
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Disease relevance of Eda


High impact information on Eda

  • We show that beta-catenin is required genetically downstream of tabby/downless and upstream of bmp and shh in placode formation [6].
  • Here, we show 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 [7].
  • We now report that EGF induces development of dermal ridges and functional sweat glands in Ta/Y hemizygotes, indicating a role in mammalian morphogenesis [8].
  • Both sequences map to the region of 10 centimorgan lying between the Tabby (Ta) and St14-1 (DxPas8) loci, close to the phosphorylase b kinase locus (Phk) [9].
  • Three of the probes map to the region between the centromere and Hprt, and two distal to Ta [10].

Chemical compound and disease context of Eda

  • The convulsant properties of methyl beta-carboline-3-carboxylate (beta-CCM) were evaluated in the TaT-fm/GncTa+/+Tfm strain carrying the tabby coat color (Ta) and/or the testicular feminization (Tfm) gene [11].

Biological context of Eda


Anatomical context of Eda

  • 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 [1].
  • 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 [12].
  • 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 [1].
  • Taken together, our results suggest that the Eda/Edar/NF-kappaB pathway exerts its effect on SMG epithelial cell proliferation, lumina formation, and histodifferentiation [14].
  • Although recent studies have focused on the role of Eda/Edar signaling during hair and tooth development, very little is known about its role during embryonic submandibular salivary gland (SMG) development [14].

Associations of Eda 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 [15].
  • To analyze their action further, we conditionally expressed the isoforms as tetracycline ('Tet')-regulated transgenes in Tabby (EDA-negative) and wild-type mice [16].
  • MATERIALS AND METHODS: Eight-week-old androgen-resistant testicular feminized male (Tfm) and Tabby control mice were orchidectomized (ORX) and treated for 4 weeks with a slow-release testosterone (T) pellet (delivering 167 microg/day) or a placebo pellet [17].
  • SETTING AND SAMPLE POPULATION: Institute of Experimental Medicine, Academy of Sciences, Prague. Heads of 75 Ta homozygous and hemizygous mice and 40 wild type (WT) control mice aged from embryonic day (ED) 14.0-20.5 (newborns), harvested during 1995-2001 [18].

Regulatory relationships of Eda


Other interactions of Eda

  • Eda supplementation induced a significant increase in SMG branching, and enhanced activation of NF-kappaB [14].
  • We have established a Mus spretus/Mus musculus domesticus interspecific backcross segregating for two X-linked mutant genes, Ta and Hyp, using in vitro fertilization [21].
  • Interactions between epidermal growth factor and the Tabby mutation in skin [4].
  • This high-density map provides probes in the vicinity of a number of important genetic loci in this region which include the X-inactivation center, the Ta locus, and the mottled (Mo) locus, and therefore provides a molecular framework for identification of the genes encoded at these loci [22].
  • Glands are completely absent in mice lacking Ectodysplasin (Eda) and Edaradd (Eda receptor adaptor protein), members of the tumor necrosis (TNF) superfamily of signaling factors [23].

Analytical, diagnostic and therapeutic context of Eda


  1. Regulation of hair follicle development by the TNF signal ectodysplasin and its receptor Edar. Laurikkala, J., Pispa, J., Jung, H.S., Nieminen, P., Mikkola, M., Wang, X., Saarialho-Kere, U., Galceran, J., Grosschedl, R., Thesleff, I. Development (2002) [Pubmed]
  2. Genetic and molecular evidence of an X-chromosome deletion spanning the tabby (Ta) and testicular feminization (Tfm) loci in the mouse. Cattanach, B.M., Rasberry, C., Evans, E.P., Dandolo, L., Simmler, M.C., Avner, P. Cytogenet. Cell Genet. (1991) [Pubmed]
  3. Effect of the X-linked gene Tabby (Ta) on eyelid opening and incisor eruption in neonatal mice is opposite to that of epidermal growth factor. Kapalanga, J., Blecher, S.R. Development (1990) [Pubmed]
  4. Interactions between epidermal growth factor and the Tabby mutation in skin. Isaacs, K., Brown, G., Moore, G.P. Exp. Dermatol. (1998) [Pubmed]
  5. Ectodysplasin has a dual role in ectodermal organogenesis: inhibition of Bmp activity and induction of Shh expression. Pummila, M., Fliniaux, I., Jaatinen, R., James, M.J., Laurikkala, J., Schneider, P., Thesleff, I., Mikkola, M.L. Development (2007) [Pubmed]
  6. beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Huelsken, J., Vogel, R., Erdmann, B., Cotsarelis, G., Birchmeier, W. Cell (2001) [Pubmed]
  7. Permanent correction of an inherited ectodermal dysplasia with recombinant EDA. Gaide, O., Schneider, P. Nat. Med. (2003) [Pubmed]
  8. Induction of sweat glands by epidermal growth factor in murine X-linked anhidrotic ectodermal dysplasia. Blecher, S.R., Kapalanga, J., Lalonde, D. Nature (1990) [Pubmed]
  9. Localization of the region homologous to the Duchenne muscular dystrophy locus on the mouse X chromosome. Heilig, R., Lemaire, C., Mandel, J.L., Dandolo, L., Amar, L., Avner, P. Nature (1987) [Pubmed]
  10. Mapping of the mouse X chromosome using random genomic probes and an interspecific mouse cross. Amar, L.C., Arnaud, D., Cambrou, J., Guenet, J.L., Avner, P.R. EMBO J. (1985) [Pubmed]
  11. A mouse mutant strain highly resistant to methyl beta-carboline-3-carboxylate-induced seizures. Clément, Y., Launay, J.M., Bondoux, D., Venault, P., Martin, B., Young, J., Robel, P., Chapouthier, G. Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale. (1996) [Pubmed]
  12. Edar/Eda interactions regulate enamel knot formation in tooth morphogenesis. Tucker, A.S., Headon, D.J., Schneider, P., Ferguson, B.M., Overbeek, P., Tschopp, J., Sharpe, P.T. Development (2000) [Pubmed]
  13. Detailed ordering of markers localizing to the Xq26-Xqter region of the human X chromosome by the use of an interspecific Mus spretus mouse cross. Avner, P., Amar, L., Arnaud, D., Hanauer, A., Cambrou, J. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  14. Ectodysplasin receptor-mediated signaling is essential for embryonic submandibular salivary gland development. Jaskoll, T., Zhou, Y.M., Trump, G., Melnick, M. The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology. (2003) [Pubmed]
  15. Ectodysplasin, Edar and TNFRSF19 are expressed in complementary and overlapping patterns during mouse embryogenesis. Pispa, J., Mikkola, M.L., Mustonen, T., Thesleff, I. Gene Expr. Patterns (2003) [Pubmed]
  16. Inducible mEDA-A1 transgene mediates sebaceous gland hyperplasia and differential formation of two types of mouse hair follicles. Cui, C.Y., Durmowicz, M., Ottolenghi, C., Hashimoto, T., Griggs, B., Srivastava, A.K., Schlessinger, D. Hum. Mol. Genet. (2003) [Pubmed]
  17. Role of the androgen receptor in skeletal homeostasis: the androgen-resistant testicular feminized male mouse model. Vandenput, L., Swinnen, J.V., Boonen, S., Van Herck, E., Erben, R.G., Bouillon, R., Vanderschueren, D. J. Bone Miner. Res. (2004) [Pubmed]
  18. Different morphotypes of the tabby (EDA) dentition in the mouse mandible result from a defect in the mesio-distal segmentation of dental epithelium. Peterková, R., Kristenová, P., Lesot, H., Lisi, S., Vonesch, J.L., Gendrault, J.L., Peterka, M. Orthodontics & craniofacial research. (2002) [Pubmed]
  19. NF-kappaB transmits Eda A1/EdaR signalling to activate Shh and cyclin D1 expression, and controls post-initiation hair placode down growth. Schmidt-Ullrich, R., Tobin, D.J., Lenhard, D., Schneider, P., Paus, R., Scheidereit, C. Development (2006) [Pubmed]
  20. Cusp patterning defect in Tabby mouse teeth and its partial rescue by FGF. Pispa, J., Jung, H.S., Jernvall, J., Kettunen, P., Mustonen, T., Tabata, M.J., Kere, J., Thesleff, I. Dev. Biol. (1999) [Pubmed]
  21. Determination of a molecular map position for Hyp using a new interspecific backcross produced by in vitro fertilization. Kay, G., Thakker, R.V., Rastan, S. Genomics (1991) [Pubmed]
  22. High-density molecular map of the central span of the mouse X chromosome. Brockdorff, N., Kay, G., Smith, S., Keer, J.T., Hamvas, R.M., Brown, S.D., Rastan, S. Genomics (1991) [Pubmed]
  23. Intercellular growth factor signaling and the development of mouse tracheal submucosal glands. Rawlins, E.L., Hogan, B.L. Dev. Dyn. (2005) [Pubmed]
  24. TNF signaling via the ligand-receptor pair ectodysplasin and edar controls the function of epithelial signaling centers and is regulated by Wnt and activin during tooth organogenesis. Laurikkala, J., Mikkola, M., Mustonen, T., Aberg, T., Koppinen, P., Pispa, J., Nieminen, P., Galceran, J., Grosschedl, R., Thesleff, I. Dev. Biol. (2001) [Pubmed]
  25. EDA targets revealed by skin gene expression profiles of wild-type, Tabby and Tabby EDA-A1 transgenic mice. Cui, C.Y., Durmowicz, M., Tanaka, T.S., Hartung, A.J., Tezuka, T., Hashimoto, K., Ko, M.S., Srivastava, A.K., Schlessinger, D. Hum. Mol. Genet. (2002) [Pubmed]
  26. Zfy is transcribed in the normal mouse epididymis and in the XXSxr ("sex reversed") testis. Mastrangelo, P., Zwingman, T., Erickson, R.P., Blecher, S.R. Dev. Genet. (1994) [Pubmed]
  27. Ectodysplasin, a protein required for epithelial morphogenesis, is a novel TNF homologue and promotes cell-matrix adhesion. Mikkola, M.L., Pispa, J., Pekkanen, M., Paulin, L., Nieminen, P., Kere, J., Thesleff, I. Mech. Dev. (1999) [Pubmed]
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