Inner ear supporting cells: rethinking the silent majority

Abstract

Sensory epithelia of the inner ear contain two major cell types: hair cells and supporting cells. It has been clear for a long time that hair cells play critical roles in mechanoreception and synaptic transmission. In contrast, until recently the more abundant supporting cells were viewed as serving primarily structural and homeostatic functions. In this review, we discuss the growing information about the roles that supporting cells play in the development, function and maintenance of the inner ear, their activities in pathological states, their potential for hair cell regeneration, and the mechanisms underlying these processes.

Fig. 1

Structural and cellular organizations of the mammalian cochlear (A) and vestibular (B) sensory epithelia. (A) The functional unit of cochlea, organ of Corti, consists of one row of inner hair cells (IHC) and three rows of outer hair cells (OHC) that are surrounded by various supporting cells identifiable by structural features and expression of markers. The organ of Corti is covered by tectorial membrane and seated onto the basilar membrane. Both inner and outer hair cells are innervated by cochlear nerves. The apical and basolateral surfaces of the cochlear sensory epithelia are immersed in endolymphic and perilymphic media, respectively. (B) Hair cells (HC) in vestibular organs are ensheathed and separated by more homogenous supporting cells (SC). Type II hair cells form typical ribbon synapses with vestibular nerve endings, whereas type I hair cells have their entire cell body wrapped by calyx nerve terminals. In utricle and saccule, the sensory epithelia are covered by otoconia which stimulate hair cells upon head motion.

Fig. 2

Diverse roles of supporting cells in developing (A) and mature (B) sensory epithelia. (A) During development, supporting cells (SC) form mosaic cellular pattern with hair cells (HC) through Notch signaling and Nectin heterophilic interactions. Supporting cells express Ptk7 which collaborate with Fz3/6 signaling to regulate planar cell polarity of hair cells. Production of ATP and neurotrophins (NTs) by supporting cells are involved in ribbon synaptogenesis. (B) In mature sensory epithelia, the apical surfaces of hair and supporting cells are sealed by connexin (Cx) tight junctions to form reticular lamina. Supporting cells mediate homeostasis of cations (Na⁺, K⁺) and small molecules (Glu, IP3) through transporters and gap junctions. Supporting cells also modulate extracellular matrices (ECM) by production of ECM components.

Fig. 3

Roles of supporting cells in injured sensory epithelia. (A) Upon hair cells (HC) damage, supporting cells (SC) may clear the damaged hair cells by expelling them to the scala media and/or phagocytose the debris of injured hair cell. The supporting cells surrounding injury site converge to re-seal the sensory epithelia to prevent further damage. (B) The damaged hair cells can be regenerated by direct transdifferentiation or mitotic proliferation of supporting cells.