Recent advances in molecular studies on cochlear development and regeneration

The auditory organ cochlea harbors two types of sound receptors, inner hair cells (IHCs) and outer hair cells (OHCs), which are innervated by spiral (auditory) ganglion neurons (SGNs). Recent transcriptomic, epigenetic, and genetic studies have started to reveal various aspects of cochlear development, including how prosensory progenitors are specified and diversified into IHCs or OHCs, as well as the heterogeneity among SGNs and how SGN subtypes are formed. Here, we primarily review advances in this line of research over the past five years and discuss a few key studies (from the past two years) to elucidate (1) how prosensory progenitors are specified; (2) the cis-regulatory control of Atoh1 expression and the synergistic interaction between Atoh1 and Pou4f3; and (3) the essential roles of Insm1 and Ikzf2 in OHC development and Tbx2 in IHC development. Moreover, we highlight the contribution of recent molecular studies on cochlear development toward the goal of regenerating IHCs and OHCs, which holds considerable potential for application in treating human deafness. Lastly, we briefly summarize the most recent progress on uncovering when and how SGN diversity is generated.