Sonic hedgehog (#Shh) is responsible for the temporal and directional control of mammalian cochlear hair cell differentiation. This study led by Prof. Sham Mai-har demonstrates that restriction of Gli2 expression, the major transcriptional activator of the Shh signaling pathway, is a prerequisite for cochlear hair cell differentiation. Gli2 blocks hair cell differentiation by maintaining the progenitor state of Sox2+ prosensory cells.

The spatiotemporal differentiation pattern of hair cells along the basal–apical axis of the cochlea is achieved by Sufu- and Spop-mediated control of Gli2 transcription in the sensory progenitor cells; cells expressing low Gli2 could differentiate, whereas cells with high Gli2 were locked in the progenitor state. This study unravels the mechanism underlying Shh-mediated control of sensory hair cell differentiation in the mammalian cochlea and contributes to the understanding of the etiology of human hearing impairment.

The findings have been published in The Proceedings of the National Academy of Sciences (#PNAS): https://www.pnas.org/doi/10.1073/pnas.2206571119.