Anatomical and physiological development of the human inner ear

•Anatomical differentiation of human vestibular hair cells begins by 8 weeks gestation.•Fetal cochlea hair cell differentiation starts two weeks after vestibular hair cells.•Afferent innervation of the neuroepithelium occurs before hair cell differentiation.•Vestibular hair cells and calyx afferent fibers are functional by mid gestation.•PAX2, SOX2, and SOX9 in human fetal cochlea show graded spatiotemporal profiles.

We describe the development of the human inner ear with the invagination of the otic vesicle at 4 weeks gestation (WG), the growth of the semicircular canals from 5 WG, and the elongation and coiling of the cochlea at 10 WG. As the membranous labyrinth takes shape, there is a concomitant development of the sensory neuroepithelia and their associated structures within. This review details the growth and differentiation of the vestibular and auditory neuroepithelia, including synaptogenesis, the expression of stereocilia and kinocilia, and innervation of hair cells by afferent and efferent nerve fibres. Along with development of essential sensory structures we outline the formation of crucial accessory structures of the vestibular system – the cupula and otolithic membrane and otoconia as well as the three cochlea compartments and the tectorial membrane. Recent molecular studies have elaborated on classical anatomical studies to characterize the development of prosensory and sensory regions of the fetal human cochlea using the transcription factors, PAX2, MAF-B, SOX2, and SOX9. Further advances are being made with recent physiological studies that are beginning to describe when hair cells become functionally active during human gestation.This article is part of a Special Issue entitled .