Conserved and Divergent Principles of Planar Polarity Revealed by Hair Cell Development and Function

Abstract

Planar polarity describes the organization and orientation of polarized cells or cellular structures within the plane of an epithelium. The sensory receptor hair cells of the vertebrate inner ear have been recognized as a preeminent vertebrate model system for studying planar polarity and its development. This is principally because planar polarity in the inner ear is structurally and molecularly apparent and therefore easy to visualize. Inner ear planar polarity is also functionally significant because hair cells are mechanosensors stimulated by sound or motion and planar polarity underlies the mechanosensory mechanism, thereby facilitating the auditory and vestibular functions of the ear. Structurally, hair cell planar polarity is evident in the organization of a polarized bundle of actin-based protrusions from the apical surface called stereocilia that is necessary for mechanosensation and when stereociliary bundle is disrupted auditory and vestibular behavioral deficits emerge. Hair cells are distributed between six sensory epithelia within the inner ear that have evolved unique patterns of planar polarity that facilitate auditory or vestibular function. Thus, specialized adaptations of planar polarity have occurred that distinguish auditory and vestibular hair cells and will be described throughout this review. There are also three levels of planar polarity organization that can be visualized within the vertebrate inner ear. These are the intrinsic polarity of individual hair cells, the planar cell polarity or coordinated orientation of cells within the epithelia, and planar bipolarity; an organization unique to a subset of vestibular hair cells in which the stereociliary bundles are oriented in opposite directions but remain aligned along a common polarity axis. The inner ear with its complement of auditory and vestibular sensory epithelia allows these levels, and the inter-relationships between them, to be studied using a single model organism. The purpose of this review is to introduce the functional significance of planar polarity in the auditory and vestibular systems and our contemporary understanding of the developmental mechanisms associated with organizing planar polarity at these three cellular levels.

The dark kinase STK32A regulates hair cell planar polarity opposite of EMX2 in the developing mouse inner ear

“…EMX2 expression is restricted to the lateral region of the utricular sensory epithelium and the inner region of the saccular sensory epithelium, and the hair cells in these regions orient their bundles such that the kinocilium is positioned adjacent to the PCP protein PK2, and opposite of Frizzled. In contrast, the kinocilium in EMX2-negative hair cells of the other regions are positioned opposite of PK2 and therefore adjacent to Frizzled (4,25,26). As a result, the vestibular maculae contain two groups of hair cells with opposite bundle orientations that meet at the LPR (Fig.…”

“…Planar polarity is seen across diverse species and tissues, and this organization is essential for early development events including left/right asymmetry in the primitive streak and coordinated cellular movements such as convergent extension and neural tube closure (1-3). Similarly, within the inner ear the function of the sensory receptor hair cells that detect sound and motion is dependent upon the development of a planar polarized bundle of elongated microvilli called stereocilia that project from the apical cell surface (4, 5). Mutant mice with disrupted planar polarity have vestibular deficits indicating that planar polarity is required for hair cell function (6, 7).…”

RGS12 polarizes the GPSM2-GNAI complex to organize and elongate stereocilia in sensory hair cells

“…As DAPLE directly binds GNAI and dishevelled homolog (DVL2) (Fig. 1B) (29), DAPLE was proposed to couple the distinct planar polarity mechanisms that regulate cytoskeleton asymmetry in single HCs (via GPSM2-GNAI) and HC orientation along the epithelial plane [via DVL2 and other planar cell polarity (PCP) proteins ensuring intercellular communication] (25,(30)(31)(32). Many questions remain unanswered, however.…”

Emerging Roles of RNA-Binding Proteins in Inner Ear Hair Cell Development and Regeneration

“…The mammalian inner ear is formed by a snail-shaped cochlea, which is essential for hearing, and by a vestibular system necessary for maintaining balance. Strikingly, both the cochlear and the vestibular epithelia display highly polarized hair cells with uniformly oriented stereociliary bundles on their apical surfaces, which is critical for auditory and vestibular mechanosensation [ 4 ]. For example, the organ of Corti in the cochlea consists of one row of inner hair cells and three rows of outer hair cells, which are separated by specialized supporting cells.…”