Canonical Wnt signaling modulates Tbx1, Eya1, and Six1 expression, restricting neurogenesis in the otic vesicle

Laina Freyer, Bernice E. Morrow

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1708-1722
Number of pages15
JournalDevelopmental Dynamics
Volume239
Issue number6
DOIs
StatePublished - 2010

Fingerprint

Catenins
Neurogenesis
Ear
DiGeorge Syndrome
Branchio-Oto-Renal Syndrome
Inner Ear
Genes
Transcription Factors
Alleles

Keywords

  • Eya1
  • Inner ear
  • Mouse models
  • Neurogenesis
  • Otic vesicle
  • Six1
  • Tbx1
  • Transcription regulation
  • Wnt
  • β-catenin

ASJC Scopus subject areas

  • Developmental Biology
  • Medicine(all)

Cite this

Canonical Wnt signaling modulates Tbx1, Eya1, and Six1 expression, restricting neurogenesis in the otic vesicle. / Freyer, Laina; Morrow, Bernice E.

In: Developmental Dynamics, Vol. 239, No. 6, 2010, p. 1708-1722.

Research output: Contribution to journalArticle

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