Canonical Wnt signaling modulates Tbx1, Eya1, and Six1 expression, restricting neurogenesis in the otic vesicle.
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.
Freyer
Laina
L
Department of Genetics, Albert Einstein College of Medicine, Bronx, New York, USA.
Morrow
Bernice E
BE
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
D014157:Transcription Factors; D051176:beta Catenin