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 -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. TeaserThe interaction between solid-like cells and fluid-like cells drives the cellular organisation in the tissue.