TitleCoupling between spatial compartments integrates morphogenetic patterning in the organ of Corti.
Publication TypeJournal Article
Year of Publication2025
AuthorsPrakash A, Raman S, Kaushik R, Manchanda P, Iyer AS, Ladher RK
JournalPLoS Biol
Volume23
Issue9
Paginatione3003350
Date Published2025 Sep
ISSN1545-7885
KeywordsAnimals, Body Patterning, Cell Polarity, Hair Cells, Auditory, Mice, Mice, Knockout, Morphogenesis, Nerve Tissue Proteins, Organ of Corti
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.

DOI10.1371/journal.pbio.3003350
Alternate JournalPLoS Biol
PubMed ID40924666
PubMed Central IDPMC12419656