Coexistence of asymmetric cell shape dynamics governs organisational diversity in sensory epithelia

Abstract

Tissues and organs develop a wide range of shapes, sizes and cellular organisations, linked to their physiological function. How developmental programmes generate this organisational diversity remains poorly understood. Inner ear sensory epithelia in birds, fish, and mammals provide a tractable system to address this question, as their constituent cells arise from a common developmental lineage, share molecular signatures, and have conserved physiological functions, yet assemble into distinct cellular organisations. These epithelia contain two principal cell types, mechanosensory hair cells (HCs) and supporting cells (SCs), organised into mosaics. Here, we developed a three-parameter morphospace that quantitatively captures epithelial organisation, enabling comparisons across species, structures and developmental stages. Combining this framework with genetic perturbation, biochemical analysis and live imaging reveals that the diverse mature organisations emerge from a common early organisational state constrained by Notch-Delta signalling. During subsequent development, the differential localisation of adhesion molecules (Cdh1,2 and Nectin) and contractility-associated proteins (NM2 and -actinin-4) at HC-SC and SC-SC junctions establishes junctional asymmetries. Across species, asymmetry drives stable circular HCs and actively remodelling SCs. The coexistence of these cell shape states drives selective intercalation, guiding each epithelium along a distinct trajectory through morphospace toward its mature organisation. These findings identify cell-shape dynamics as a developmental mechanism for generating organisational diversity in sensory, and potentially other, epithelia.