When tissues collide: A bilayer cellular Potts model of epithelial fusion

Fusion of two epithelial sheets is a common motif in morphogenesis with examples including Drosophila dorsal closure, palate fusion, neural tube closure, and choroid fissure closure. The mechanisms of this type of fusion are not yet fully understood but appear to involve adhesion agents such as cadherins, filopodia, and lamellipodia that promote matching of cell shapes in the apposed sheets. In this talk we introduce a bilayer cellular Potts model (CPM) in which two planar epithelial sheets are coupled in the direction perpendicular to their surfaces as opposed to the in plane coupling seen in wound healing models. The new, biologically motivated coupling lowers the system energy when a cell edge in one layer aligns with a cell edge in the other layer. A Monte Carlo method is used to evolve the system under the influence of an effective temperature. Rich dynamics occur in this model due to an interplay between the new bilayer coupling and the unjamming transition in the individual layers. In particular, we find that fusion does not progress smoothly, but in jumps that depend on conditions favorable for T1 transitions. Further, fusion is maximized over a range of cell shape indices near the critical shape index for unjamming, and oscillations in the degree of fusion are observed at the lower end of this range. We compare our model predictions to spatiotemporal analysis of choroid fissure closure in the developing zebrafish eye and find that the model shows promise in illuminating certain aspects of this biological process.