Lead roles for supporting actors: critical functions of inner ear supporting cells

Abstract

Many studies that aim to investigate the underlying mechanisms of hearing loss or balance disorders focus on the hair cells and spiral ganglion neurons of the inner ear. Fewer studies have examined the supporting cells that contact both of these cell types in the cochlea and vestibular end organs. While the roles of supporting cells are still being elucidated, emerging evidence indicates that they serve many functions vital to maintaining healthy populations of hair cells and spiral ganglion neurons. Here we review recent studies that highlight the critical roles supporting cells play in the development, function, survival, death, phagocytosis, and regeneration of other cell types within the inner ear. Many of these roles have also been described for glial cells in other parts of the nervous system, and lessons from these other systems continue to inform our understanding of supporting cell functions. This article is part of a Special Issue entitled "Annual Reviews 2013".

Keywords: BDNF; ERK 1/2; FGF; GLAST; HSP70; IHC; ISC; NRG; NT3; PS; SGN; T-cell restricted intracellular antigen-related protein; TEM; TIAR; brain-derived neurotrophic factor; extracellularly regulated kinases 1 and 2; fibroblast growth factor; glutamate aspartate transporter; heat shock protein 70; inner hair cell; inner supporting cell; neuregulin; neurotrophin-3; phosphatidylserine; spiral ganglion neuron; transmission electron microscopy.

Figure 1

Supporting cells and glia provide trophic factors to neurons and clear glutamate from the synapse. Left panel, Hair cells (blue) synapse with spiral ganglion neurons (gray), and are surrounded by supporting cells (green). Hair cells release glutamate, which is cleared from the synapse by glutamate receptors expressed by supporting cells. Spiral ganglion neurons express NRG, which binds to erbB receptors located on the supporting cells, thereby promoting SGN survival. Right panel, illustration of a tripartite synapse between two neurons (gray) and an astrocyte (green). The presynaptic neuron (top) releases glutamate into the synapse, which is cleared from the synapse by glutamate receptors on the astrocyte. Neurons also express NRG, which binds to erbB receptors located on the astrocyte, an interaction necessary for normal astroglial morphology and neuronal migration.

Figure 2

Supporting cells and glia eliminate dead cells. Left panel, illustration of supporting cell processes (arrowheads) invading a neighboring hair cell (blue) during the process of hair bundle excision. Phosphatidylserine (PS, red outline) exposure is restricted the apical membrane of the hair cell, but its interaction with a PS receptor on neighboring supporting cells is unclear. Right panel, illustration of a neuron (gray) as a microglia (green) approaches for phagocytosis. The damaged neuron exposes PS, which binds a PS receptor expressed by the microglia.

Figure 3

Supporting cells and glia mediate the regeneration of dead cells. Left panel, illustration of supporting cells (green) acting as progenitors for regenerated hair cells (blue). Supporting cells can replace damaged hair cells and supporting cells through mitotic regeneration. Alternatively, supporting cells can replace hair cells by direct transdifferentiation. Right panel, illustration of Müller glia (green) dividing to replace damaged photoreceptors (blue).