and act in concert to modulate the fate of neurosensory cells of the mouse otic vesicle.

The domain within the otic vesicle (OV) known as the neurosensory domain (NSD), contains cells that will give rise to the hair and support cells of the otic sensory organs, as well as the neurons that form the cochleovestibular ganglion (CVG). The molecular dynamics that occur at the NSD boundary relative to adjacent OV cells is not well defined. The transcription factor gene expression pattern is complementary to the NSD, and inactivation results in expansion of the NSD and expression of the Notch ligand, Jag1 mapping, in part of the NSD. To shed light on the role of in NSD development, as well as to test whether and might genetically interact to regulate this process, we inactivated within the expression domain using a knock-in allele. We observed an enlarged neurogenic domain marked by a synergistic increase in expression of and other proneural transcription factor genes in double and conditional loss-of-function embryos. We noted that neuroblasts preferentially expanded across the medial-lateral axis and that an increase in cell proliferation could not account for this expansion, suggesting that there was a change in cell fate. We also found that inactivation of with resulted in failed development of the cristae and semicircular canals, as well as notably fewer hair cells in the ventral epithelium of the inner ear rudiment when inactivated on a null background, compared to mutant embryos. We propose that loss of expression of and within the expression domain tips the balance of cell fates in the NSD, resulting in an overproduction of neuroblasts at the expense of non-neural cells within the OV.