Junctional Heterogeneity Shapes Epithelial Morphospace

Combination of genetic, biochemical and mechanical cues can theoretically generate any shapes and cellular organisation of an organ. From this vast possible organisation called morphospace , an unknown mechanism governs the diverse organisation of epithelia. We investigated this mechanism using the mechanosensory epithelia of fish, birds, and mammals. These epithelia have two cell types: mechanosensory hair cells (HCs) and supporting cells (SCs). Across these epithelia, HC and SC share a similar developmental lineage and molecular signatures but organise differently, making it an ideal system. Using a quantitative, morphospace framework we show the large diversity in sensory epithelia develops from a small overlapping initial state. This initial state with small, circular HCs surrounded by larger SCs is governed by Notch–Delta signalling. As development proceeds, the differential recruitment of Cdh2, Nectin, and α-actinin-4 generates a junctional heterogeneity. This junctional heterogeneity induces a cell-type selective jamming transition: HCs become mechanically jammed while SCs remain fluid-like. This cell-type-specific mechanical state drives differential intercalation, leading to the differential organisation. By regulating this transition of cellular state, epithelia are guided towards their morphospace. Our work proposes the cell-type specific mechanical state and the genetic constrains as mechanism that drives patterning of mechano-sensory epithelia and potentially others.