Lien vers Pubmed [PMID] – 20503367
Dev. Dyn. 2010 Jun;239(6):1708-22
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.