title: Tooth patterning and enamel formation can be manipulated by misexpression of TNF receptor Edar.
abstract: Signaling by Edar, a tumor necrosis factor receptor, is required for the development of ectodermal organs. Mutations in Edar or other molecules of the same signaling pathway cause ectodermal dysplasias in humans and mice. In these diseases, teeth are missing or malformed, and the development of hairs and several glands is hypoplastic. During tooth and hair development, Edar expression becomes patterned to ectodermal placodes and signaling centers. This localization has been suggested to be required for organogenesis. We have expressed Edar throughout the ectoderm using the keratin 14 promoter and show that this misexpression disrupts tooth patterning and differentiation. Tooth shape and cusp number are differentially affected, depending on the amount of transgene expression. In addition, tooth enamel formation is defective in a dose-dependent manner. We speculate that the tooth patterning defects are caused by ectopic Edar activity outside the signaling centers.
authors.affiliation: Developmental Biology Programme, Institute of Biotechnology, Viikki Biocenter, University of Helsinki, Helsinki, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Pispa
authors.forename: Tuija
authors.initials: T
authors.lastname: Mustonen
authors.forename: Marja L
authors.initials: ML
authors.lastname: Mikkola
authors.forename: Aapo T
authors.initials: AT
authors.lastname: Kangas
authors.forename: Petra
authors.initials: P
authors.lastname: Koppinen
authors.forename: Pirjo-Liisa
authors.initials: PL
authors.lastname: Lukinmaa
authors.forename: Jukka
authors.initials: J
authors.lastname: Jernvall
authors.forename: Irma
authors.initials: I
authors.lastname: Thesleff
mesh_terms: D000566:Amelogenesis / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D003743:Dental Enamel / Q000196:embryology* / Q000378:metabolism; D053339:Edar Receptor; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D053547:Keratin-14; D007633:Keratins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011401:Promoter Regions, Genetic; D053338:Receptors, Ectodysplasin; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014070:Tooth / Q000033:anatomy & histology* / Q000196:embryology* / Q000378:metabolism; D019076:Transgenes
chemical_list: C506008:EDAR protein, human; D053339:Edar Receptor; C506009:Edar protein, mouse; C507540:KRT14 protein, human; D053547:Keratin-14; C507446:Krt14 protein, mouse; D008565:Membrane Proteins; D053338:Receptors, Ectodysplasin; D018124:Receptors, Tumor Necrosis Factor; D007633:Keratins