Modeling choroid fissure closure by coupling two cellular Potts models*

Choroid fissure closure (CFC) is an important part of vertebrate eye morphogenesis that is not yet fully understood. During CFC, two separate neuroepithelial apical surfaces approach each other and fuse into one, forming a continuous ventral optic cup. Failure of this process can result in a coloboma, associated with 3-11% of reports of childhood blindness. In this work we create a new biomechanical model of CFC by extending the Cellular Potts Model (CPM). The basic CPM considers a two-dimensional slice through a generic epithelial tissue and models cadherin-mediated cell-cell adhesion, active contractility of the actin-myosin cortex, and membrane fluctuations (via an effective temperature). Energy changes due to cellular processes such as T1 transitions are computed, and the system is evolved towards states that minimize the total energy. Specifically, we introduce a novel “bilayer CPM” that couples two basic CPMs together via out-of-plane binding between adhesion agents residing at cell edges, and tests the hypothesis that CFC fusion depends on the individual layers being in a parametric sweet spot between fluid-like and solid-like regimes. Mapping out the behavioral regimes of the bilayer CPM indeed reveals a sweet spot for fusion among other behaviors such as possible oscillations in the degree of fusion as a function of the individual layers’ cell shape index. These oscillations potentially mimic those observed during development of the zebrafish eye.