Exploring morphological changes in supporting cell: new cell polarity perspective and approaches - PROJECT SUMMARY Cell polarity mechanisms are essential for shaping the morphology and orientation of hair cells in the inner ear, ensuring proper sensory function. Communication at apical junctions between hair cells and their glial neighbors, the supporting cells, is particularly important for proper hair cell orientation. While supporting cells are known to relay polarity signals between hair cells, the possible influence of polarity mechanisms on their own differentiation is not well-studied. Pillar and Deiter's cells, specific types of supporting cells, have a complex and asymmetrical morphology beneath the epithelial surface. These cells develop apical extensions called phalangeal processes, which interdigitate between hair cells and play a critical scaffolding role in cochlear amplification and thus auditory function. The proposed research hypothesizes that mouse Pillar and Deiter's cells acquire their phalangeal processes through a postnatal polarization program similar to the polarization of hair bundles in hair cells. Preliminary results suggest that the basal body of supporting cells is planar-polarized and can exhibit a highly dynamic behavior during development. We aim to track the position of the basal body in supporting cells from embryogenesis to adulthood, correlate its position with the emergence of dense microtubule arrays in the underlying phalangeal process, and investigate defects in one relevant cell polarity mutant context. Additionally, we aim to develop methods for sparse labeling of supporting cells to track their individual morphology and analyze structural changes during phalangeal process development. Examining the polarization of supporting cells offers a novel perspective to address their complex remodeling, a neglected aspect of auditory science where new approaches and tools have potential for significant discoveries. Beyond providing a better fundamental understanding of supporting cell development, this groundwork will enable the analysis of morphometric changes in mutants causing congenital hearing loss. This work also has broader potential for studying supporting cell integrity in various conditions including aging and trauma such as noise damage.
