SummaryUnder conditions of homeostasis, dynamic changes in the length of individual adherens junctions (AJs) provide epithelia with the fluidity required to maintain tissue integrity in the face of intrinsic and extrinsic forces. While the contribution of AJ remodeling to developmental morphogenesis has been intensively studied, less is known about AJ dynamics in other circumstances. Here, we study AJ dynamics in an epithelium that undergoes a gradual increase in packing order, without concomitant large-scale changes in tissue size or shape. We find that neighbor exchange events are driven by stochastic fluctuations in junction length, regulated in part by junctional actomyosin. In this context, the developmental increase of isotropic junctional actomyosin reduces the rate of neighbor exchange, contributing to tissue order. We propose a model in which the local variance in tension between junctions determines whether actomyosin-based forces will inhibit or drive the topological transitions that either refine or deform a tissue.

Morphogen gradients provide positional information during development. To uncover the minimal requirements for morphogen gradient formation, we have engineered a synthetic morphogen in Drosophila wing primordia. We show that an inert protein, green fluorescent protein (GFP), can form a detectable diffusion-based gradient in the presence of surface-associated anti-GFP nanobodies, which modulate the gradient by trapping the ligand and limiting leakage from the tissue. We next fused anti-GFP nanobodies to the receptors of Dpp, a natural morphogen, to render them responsive to extracellular GFP. In the presence of these engineered receptors, GFP could replace Dpp to organize patterning and growth in vivo. Concomitant expression of glycosylphosphatidylinositol (GPI)–anchored nonsignaling receptors further improved patterning, to near–wild-type quality. Theoretical arguments suggest that GPI anchorage could be important for these receptors to expand the gradient length scale while at the same time reducing leakage.

Homophilic interactions between E-Cadherin molecules generate adhesive interfaces or junctions (AJs) that connect neighbouring cells in epithelial monolayers. These are highly dynamic structures. Under conditions of homeostasis, changes in the length of individual interfaces provide epithelia with the fluidity required to maintain tissue integrity in the face of cell division, delamination and extrinsic forces. Furthermore, when acted upon by polarized actomyosin-based forces, changes in AJ length can also drive neighbour exchange to reshape an entire tissue. Whilst the contribution of AJ remodelling to developmental morphogenesis has been subjected to intensive study, less is known about AJ dynamics in other circumstances. Here, using a combination of experiment and computational modelling, we study AJ dynamics in an epithelium that undergoes a gradual increase in packing order without concomitant large-scale changes in tissue shape or size. Under these conditions, we find that neighbour exchange events are driven by stochastic fluctuations in junction length, which are regulated at least in part by the level of junctional actomyosin. As a result of this behaviour, the steady increase in junctional actomyosin and consequent tension that accompanies development steadily reduces the rate of neighbour exchange and orders the tissue. This leads us to propose a model in which topological transitions, that underpin tissue fluidity, are either inhibited or biased by actomyosin-based forces, to drive, respectively, tissue ordering or deformation.

How biological form emerges from cell fate decisions and tissue remodelling is a fundamental question in development biology. However, an understanding of how these processes operate side-by-side to set precise and robust patterns is largely missing. Here, we investigate this interplay during the process of vein refinement in the Drosophila pupal wing. By following reporters of signalling activity dynamically, together with tissue flows, we show that longitudinal vein refinement arises from a combination of local tissue deformation and cell fate adjustments controlled by a signalling network involving Notch, Dpp, and EGFR. Perturbing large-scale convergence and extension tissue flows does not affect vein refinement, showing that pre-patterned vein domains are able to intrinsically refine to the correct width. A minimal biophysical description taking into account key signalling interactions recapitulates the intrinsic tissue ability to establish a thin, regular vein independently of large-scale tissue flows. Supporting this prediction, artificial proveins optogenetically generated orthogonal to the axis of wing elongation refine against large-scale flows. Overall, we find that signalling-mediated updating of cell fate is a key contributor to reproducible patterning.

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