Regulation of cell fate in the sensory epithelia of the inner ear

The first step in the development of inner ear sensory epithelia is the specification of prosensory patches. The factors that regulate the specification of the prosensory patches have not been fully determined, but signalling through Bmp4, jagged 1/Notch, Tbx1 and Sox2 clearly has an important role in this process.Hair cells and supporting cells located in sensory epithelia in each of the auditory and vestibular regions develop with distinct cellular phenotypes. Until recently, with the exception of regional patterning genes that regulate the global patterning of the entire otocyst, the factors that determine whether a prosensory patch develops as auditory or vestibular were unknown.A recent study showed that forced activation of the canonical WNT pathway in an auditory prosensory patch is sufficient to induce hair cells and supporting cells in that patch to develop as vestibular rather than auditory.The regulation of cell cycle exit in the inner ear involves many of the same signalling molecules, such as RB1 and p27kip1, as other systems.One intriguing aspect of the development of the mammalian cochlea, the counter gradients of terminal mitosis and cellular differentiation, seems to be uniquely regulated by expression of p27kip1.The first cell type to be specified in each prosensory patch is the mechanosensory hair cell. Expression of the atonal homolog, Atoh1, is a key step in the specification of hair cells.There is some debate about the role of ATOH1 as either a commitment factor or a differentiation factor, but there is clear data to demonstrate that ATOH1 is both necessary and sufficient for hair cell formation.Developing hair cells generate at least two distinct signals that influence supporting cell development: an inhibitory signal, mediated through the Notch pathway, that prevents the cells from becoming hair cells and an inductive signal that recruits the cells to develop as supporting cells.The demonstration that forced expression of Atoh1 is sufficient to induce development of hair cells and supporting cells even outside of prosensory patches has raised the possibility that the prosensory patch hypothesis should be reconsidered.