title: Canonical Wnt signaling modulates Tbx1, Eya1, and Six1 expression, restricting neurogenesis in the otic vesicle.
abstract: To understand the mechanism by which canonical Wnt signaling sets boundaries for pattern formation in the otic vesicle (OV), we examined Tbx1 and Eya1-Six1 downstream of activated beta-catenin. Tbx1, the gene for velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS), is essential for inner ear development where it promotes Bmp4 and Otx1 expression and restricts neurogenesis. Using floxed beta-catenin gain-of-function (GOF) and loss-of-function (LOF) alleles, we found Tbx1 expression was down-regulated and maintained/enhanced in the two mouse mutants, respectively. Bmp4 was ectopically expressed and Otx1 was lost in beta-catenin GOF mutants. Normally, inactivation of Tbx1 causes expanded neurogenesis, but expression of NeuroD was down-regulated in beta-catenin GOF mutants. To explain this paradox, Eya1 and Six1, genes for branchio-oto-renal (BOR) syndrome were down-regulated in the OV of beta-catenin GOF mutants independently of Tbx1. Overall, this work helps explain the mechanism by which Wnt signaling modulates transcription factors required for neurogenesis and patterning of the OV.
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Laina
authors.initials: L
authors.lastname: Freyer
authors.forename: Bernice E
authors.initials: BE
authors.lastname: Morrow
mesh_terms: D000818:Animals; D019280:Branchio-Oto-Renal Syndrome / Q000235:genetics / Q000378:metabolism; D004062:DiGeorge Syndrome / Q000235:genetics / Q000378:metabolism; D004423:Ear / Q000502:physiology*; D004622:Embryo, Mammalian; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000235:genetics; D055495:Neurogenesis; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D014157:Transcription Factors; D051176:beta Catenin