title: Expression of Foxi3 is regulated by ectodysplasin in skin appendage placodes.
abstract: BACKGROUND
  Foxi3 is a member of the large forkhead box family of transcriptional regulators, which have a wide range of biological activities including manifold developmental processes. Heterozygous mutation in Foxi3 was identified in several hairless dog breeds characterized by sparse fur coat and missing teeth. A related phenotype called hypohidrotic ectodermal dysplasia (HED) is caused by mutations in the ectodysplasin (Eda) pathway genes.
  
  
  RESULTS
  Expression of Foxi3 was strictly confined to the epithelium in developing ectodermal appendages in mouse embryos, but no expression was detected in the epidermis. Foxi3 was expressed in teeth and hair follicles throughout embryogenesis, but in mammary glands only during the earliest stages of development. Foxi3 expression was decreased and increased in Eda loss- and gain-of-function embryos, respectively, and was highly induced by Eda protein in embryonic skin explants. Also activin A treatment up-regulated Foxi3 mRNA levels in vitro.
  
  
  CONCLUSIONS
  Eda and activin A were identified as upstream regulators of Foxi3. Foxi3 is a likely transcriptional target of Eda in ectodermal appendage placodes suggesting that HED phenotype may in part be produced by compromised Foxi3 activity. In addition to hair and teeth, Foxi3 may have a role in nail, eye, and mammary, sweat, and salivary gland development.
authors: Developmental Biology Program, Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors: Vera
authors: V
authors: Shirokova
authors: Maria
authors: M
authors: Jussila
authors: Marjo K
authors: MK
authors: Hytönen
authors: Nina
authors: N
authors: Perälä
authors: Cord
authors: C
authors: Drögemüller
authors: Tosso
authors: T
authors: Leeb
authors: Hannes
authors: H
authors: Lohi
authors: Kirsi
authors: K
authors: Sainio
authors: Irma
authors: I
authors: Thesleff
authors: Marja L
authors: ML
authors: Mikkola
mesh_terms: D028341:Activins / Q000378:metabolism*; D000818:Animals; D004285:Dogs; D053331:Ectodysplasins / Q000378:metabolism*; D004848:Epithelium / Q000196:embryology; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006197:Hair / Q000196:embryology; D006579:Heterozygote; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D015398:Signal Transduction; D012867:Skin / Q000196:embryology*; D013997:Time Factors; D014070:Tooth / Q000196:embryology*; D014158:Transcription, Genetic
chemical_list: D053331:Ectodysplasins; D051858:Forkhead Transcription Factors; C585346:Foxi3 protein, mouse; C422405:activin A; D028341:Activins