The quest for restoring hearing: Understanding ear development more completely

Abstract

Neurosensory hearing loss is a growing problem of super-aged societies. Cochlear implants can restore some hearing, but rebuilding a lost hearing organ would be superior. Research has discovered many cellular and molecular steps to develop a hearing organ but translating those insights into hearing organ restoration remains unclear. For example, we cannot make various hair cell types and arrange them into their specific patterns surrounded by the right type of supporting cells in the right numbers. Our overview of the topologically highly organized and functionally diversified cellular mosaic of the mammalian hearing organ highlights what is known and unknown about its development. Following this analysis, we suggest critical steps to guide future attempts toward restoration of a functional organ of Corti. We argue that generating mutant mouse lines that mimic human pathology to fine-tune attempts toward long-term functional restoration are needed to go beyond the hope generated by restoring single hair cells in postnatal sensory epithelia. The organ of Corti develops from a regular mosaic of hair cells surrounded by supporting cells (E14.5). Transforming this regular arrangement requires cellular reshuffling. Outer pillar cells (OP) form a row next to inner pillar cells (IP). Outer hair cells (OHC) alternate with Deiters' cells (D) and inner hair cells (IHC) alter their position relative to inner phalangeal cell (IPC).