Evolutionary and Developmental Biology Provide Insights Into the Regeneration of Organ of Corti Hair Cells

Abstract

We review the evolution and development of organ of Corti hair cells with a focus on their molecular differences from vestibular hair cells. Such information is needed to therapeutically guide organ of Corti hair cell development in flat epithelia and generate the correct arrangement of different hair cell types, orientation of stereocilia, and the delayed loss of the kinocilium that are all essential for hearing, while avoiding driving hair cells toward a vestibular fate. Highlighting the differences from vestibular organs and defining what is known about the regulation of these differences will help focus future research directions toward successful restoration of an organ of Corti following long-term hair cell loss.

Neuronal Migration Generates New Populations of Neurons That Develop Unique Connections, Physiological Properties and Pathologies

“…Unfortunately, identifying the unique function of Gata3 in inner efferent guidance and migration requires unique deletion only in the inner ear efferents as Gata3 is also essential for cochlear development (Duncan and Fritzsch, 2013). The cochlea is the most derived target of inner ear efferents that has evolved a unique motor to enhance minute cochlear vibrations needed for sound amplification (Dallos et al, 2008; Elliott et al, 2018). One molecularly underexplored separation is the segregation of different sub-populations of neurons of the olivo-cochlear efferent system.…”

Auditory Nomenclature: Combining Name Recognition With Anatomical Description

“…Equivalent cells of the outer and inner section are in different shades of the same color. Modified after Elliott et al (2018) and Lim (1986) .…”

“…For example, sound stimulation of the organ of Corti was long been depicted as a simple up-down movement that directly caused shearing forces of the tectorial membrane on the inner hair cell stereocilia ( Lewis et al, 1985 ). In contrast, more recent work suggest that the adult inner hair cell is not connected to the tectorial membrane ( Lim, 1986 ) but acts as a hydrodynamic receptor monitoring endolymph flow in and out of the subtectorial space ( Elliott et al, 2018 ).…”

“…Past research has stepwise improved the understanding of how sound moves the basilar membrane/organ of Corti/tectorial membrane complex to provide topology specific amplification ( Ren et al, 2016 ; Dewey et al, 2018 ), including a detailed understanding of the function of the cochlear amplifier in the three rows of outer hair cells ( Xia et al, 2018 ). Increasingly detailed insights into the function of the various sections of the organ of Corti have revealed major distinctions as an outer section playing a role in sound amplification and an inner section playing a role in sound conversion ( Elliott et al, 2018 ). Molecular signatures that highlight nearly all outer section cells, including the inner pillar cells, such as Prox1, have been described ( Fritzsch et al, 2010 ) that set the organ of Corti apart from vestibular sensory epithelia ( Bermingham-McDonogh et al, 2006 ).…”

Complementary and distinct roles of autophagy, apoptosis and senescence during early inner ear development

“…The ventral otocyst contains neurosensory progenitors whose stepwise specification and differentiation has been a classic model to understand basic developmental mechanisms (Torres and Giráldez, 1998;Stojanova et al, 2016). There is also a great interest in understanding otic developmental clues to achieve in vitro reproduction of the differentiation of auditory cells for the translation of this knowledge to hearing loss regenerative therapy (Hawkins et al, 2007;Groves et al, 2013;Elliott et al, 2018).…”