The function of Tbx2 and Tbx3 in regulation of morphogenesis and sensory cell differentiation in the murine inner ear

Abstract

Analysis of conditional loss-of-function mutants demonstrated that Tbx2 and Tbx3 are individually and combinatorially required for the morphogenesis of the vestibular and cochlear components of the inner ear by patterning the early otocyst. TBX2 restricts the neurogenic domain to the anterior-ventral aspect of the otic epithelium by repressing Fgf8 and maintaining Tbx1 expression in the posterior-ventral otocyst. Conditional inactivation of Tbx2 in prosensory cells prior to the onset of differentiation, caused a complete conversion of IHCs to OHCs, whereas Tbx2 misexpression led to an increased number of IHCs at the expense of OHCs. Similar changes were observed in the underlying supporting cells. Transcriptional profiling and RNA in situ hybridization analyses suggest that TBX2 regulates the specification of inner hair and supporting cells by repressing Fgfr3-mediated signalling. Hair cell-specific inactivation or misexpression of Tbx2 shortly after birth caused a cell-autonomous transdifferentiation of hair cells. These results identifying TBX2 as a crucial regulator of otic neurogenesis and sensory cell diversification.