TBX1 is required for inner ear morphogenesis

Francesca Vitelli, Antonella Viola, Masae Morishima, Tiziano Pramparo, Antonio Baldini, Elizabeth Lindsay

Research output: Contribution to journalArticlepeer-review


TBX1 is thought to be a critical gene in the pathogenesis of del22q11/DiGeorge syndrome (DGS). Morphological abnormalities of the external ear and hearing impairment (conductive or sensorineural) affect the majority of patients. Here we show that homozygous mutation of the mouse homolog Tbx1 is associated with severe inner ear defects that prevent the formation of the cochlea and of the vestibulum. Consistent with phenotypic abnormalities, Tbx1 is expressed early in otocyst development in the otic epithelium and in the periotic mesenchyme. Tbx1 loss-of-function blocks inner ear development at early otocyst stage and after neurogenesis. Analysis of chimeras suggests that Tbx1 function is required in the otic epithelium cell autonomously, but abnormalities of the periotic mesenchyme indicate that the pathogenesis of the inner ear phenotype is complex. We propose a model where Tbx1 is required for expansion of a subpopulation of otic epithelial cells, which is required to form the vestibular and auditory organs. Our data suggest that Tbx1 deletion in del22q11 patients may cause not only external and middle ear defects but also sensorineural and vestibular phenotypes observed in these patients.

Original languageEnglish
Pages (from-to)2041-2048
Number of pages8
JournalHuman Molecular Genetics
Issue number16
Publication statusPublished - Aug 15 2003

ASJC Scopus subject areas

  • Genetics


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