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 β-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 β-catenin gain-offunction (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 β-catenin GOF mutants. Normally, inactivation of Tbx1 causes expanded neurogenesis, but expression of NeuroD was down-regulated in β-catenin GOF mutants. To explain this paradox, Eya1 and Six1, genes for branchio-oto-renal (BOR) syndrome were down-regulated in the OV of β-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.
Original language | English (US) |
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Pages (from-to) | 1708-1722 |
Number of pages | 15 |
Journal | Developmental Dynamics |
Volume | 239 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2010 |
Keywords
- Eya1
- Inner ear
- Mouse models
- Neurogenesis
- Otic vesicle
- Six1
- Tbx1
- Transcription regulation
- Wnt
- β-catenin
ASJC Scopus subject areas
- Developmental Biology