Transcriptional control of neuronal maintenance by SOX2 during inner ear innervation

The cochlear sensory epithelium and its associated spiral ganglion neurons arise from a common pool of otic progenitors and must develop in synchrony to ensure proper innervation and hearing function. The transcription factor SOX2 is essential for sensory progenitor specification and hair cell differentiation, but its broader role in coordinating epithelial and neuronal development remains unclear. Here, we examined the consequences of conditional Sox2 deletion in the cochlear epithelium during prosensory development. Loss of Sox2 resulted in severe defects in peripheral axon projections and increased neuronal death within the spiral ganglion, indicating a non-cell-autonomous requirement for epithelial Sox2 in neuronal maintenance. Transcriptomic and chromatin profiling revealed that neurotrophic factors, including NTF3 and BDNF, are downstream targets of SOX2, suggesting that SOX2-dependent neurotrophin expression mediates epithelial-to-ganglionic signalling. These findings identify a transcriptional mechanism by which SOX2 coordinates the development of epithelial and neuronal compartments in the cochlea, revealing an unexpected regulatory link between sensory epithelium maturation and ganglion survival.