@article {160482, title = {Coupling between spatial compartments integrates morphogenetic patterning in the organ of Corti.}, journal = {PLoS Biol}, volume = {23}, year = {2025}, month = {2025 Sep}, pages = {e3003350}, abstract = {

Morphogenetic information arises from a combination of genetically encoded cellular properties and emergent cellular behaviors. The spatio-temporal implementation of this information is critical to ensure robust, reproducible tissue shapes, yet the principles underlying its organization remain unknown. We investigated this principle using the mouse auditory epithelium, the organ of Corti (OC). OC consists of a sensory domain, which transduces sound through polar mechanosensory hair cells (HC), part of a mosaic with supporting cells (SC). On either side of the sensory domain are non-sensory domains. These domains undergo cellular rearrangements, which, together, lead to a spiral cochlea that contains planar polarized HCs. This makes the mammalian cochlea a compelling system to understand coordination across spatial scales. Using genetic and ex vivo approaches, we found patterning of OC into sensory and non-sensory domains is associated with a combinatorial expression of adhesion molecules, which underpins OC into spatially defined compartments, enabling planar cell polarity (PCP) cues to regulate compartment-specific organization. Through compartment-specific knockouts of the PCP protein, Vangl2, we find evidence of compartment coupling, a non-linear influence on the organization within one compartment when cellular organization is disrupted in another. In the OC, compartment coupling originates from vinculin-dependent junctional mechanics, coordinating cellular dynamics across spatial scales.

}, keywords = {Animals, Body Patterning, Cell Polarity, Hair Cells, Auditory, Mice, Mice, Knockout, Morphogenesis, Nerve Tissue Proteins, Organ of Corti}, issn = {1545-7885}, doi = {10.1371/journal.pbio.3003350}, author = {Prakash, Anubhav and Raman, Sukanya and Kaushik, Raman and Manchanda, Pallavi and Iyer, Anton S and Ladher, Raj K} } @article {156898, title = {Junctional force patterning drives both positional order and planar polarity in the auditory epithelia.}, journal = {Nat Commun}, volume = {16}, year = {2025}, month = {2025 Apr 26}, pages = {3927}, abstract = {

Tissue function depends on the precise organisation of the constituent cells. In the cochlea, the fidelity of hearing depends on mechanosensory hair cells being consistently surrounded by supporting cells. In addition to this positional order, auditory sensitivity depends crucially on planar cell polarity. This is characterised by the alignment of the orientation of eccentrically placed hair bundles on each hair cell. These two levels of order emerge simultaneously despite the cellular fluxes that occur during cochlear development. However, the link between tissue-scale cellular rearrangements and intrinsic cellular mechanisms remains unknown. By combining experimental and theoretical approaches, we find a precise force patterning underpinning positional order and planar cell polarity. This occurs through the modulation of the levels and phospho-type of the regulatory light chain of non-muscle myosin II at specific cell-cell junctions of the auditory epithelium. We propose that the control of junctional mechanics is vital for the organisation of multi-cell-type epithelia.

}, keywords = {Animals, Cell Polarity, Cochlea, Epithelium, Hair Cells, Auditory, Intercellular Junctions, Mice, Myosin Light Chains, Myosin Type II}, issn = {2041-1723}, doi = {10.1038/s41467-025-58557-0}, url = {https://www.nature.com/articles/s41467-025-58557-0}, author = {Prakash, Anubhav and Weninger, Julian and Singh, Nishant and Raman, Sukanya and Rao, Madan and Kruse, Karsten and Ladher, Raj K} } @article {159724, title = {Role of Pcdh15 in the development of intrinsic polarity of inner ear hair cells.}, journal = {PLoS Genet}, volume = {21}, year = {2025}, month = {2025 Aug}, pages = {e1011825}, abstract = {

In vertebrates, auditory information is transduced in the cochlea by mechanosensory hair cells (HC) through an eccentrically organised structure known as the hair bundle. This consists of a true cilium, known as the kinocilium, and modified microvilli, known as stereocilia. The hair bundle has a distinct structure with stereocilia organised in graded rows, with the longest abutting the kinocilium. The hair bundles of all HC are aligned to the tissue axis and are planar polarised. Important in the development and physiology of HC are protein bridges consisting of cadherin-23 (CDH23) and protocadherin-15 (PCDH15). These link the tips of stereocilia, where they play a role in mechanotransduction, and between the kinocilia and the stereocilia, where they are involved in development. Both Cdh23 and Pcdh15 mutations result in defects in planar polarity; however, the mechanism through which this defect arises is unclear. Using a novel mutant for the Pcdh15-CD2 isoform, we show that while the initial deflection of the kinocilium occurs, its peripheral migration to register with Gαi is perturbed. Pcdh15-CD2 genetically interacts with Gpsm2, perturbing vestibular function. We find that the earliest expression of PCDH15-CD2 is at the base of the kinocilia, and the defects in morphogenesis occur before the formation of kinocilial links. By re-introducing functional PCDH15-CD2, we show that polarity can be restored. Our data suggest that, in addition to its adhesive role, PCDH15-CD2 has an early role in intrinsic hair cell polarity through a mechanism independent of kinocilial links.

}, keywords = {Animals, Basal Bodies, Cadherin Related Proteins, Cell Polarity, Ear, Inner, Gene Knock-In Techniques, Hair Cells, Auditory, Mice, Mutation, Phosphorylation, Protein Domains, Protein Precursors, Tyrosine}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1011825}, author = {Kaushik, Raman and Pandey, Shivangi and Prakash, Anubhav and Ganatra, Fenil and Abe, Takaya and Kiyonari, Hiroshi and Ladher, Raj K} }