A lateral tension model for cranial mouse neural tube closure

Embryos fold their tissues into increasingly complicated shapes during development. Cells produce and coordinate the forces needed to fold tissues through networks of F-actin and Myosin II (actomyosin). We can discern the mechanical mechanisms used to fold tissues by analyzing these networks. Apical actomyosin is required to fold the neuroepithelium (NE), with a midline hinge and lateral neural folds into the neural tube. However, the large size and complex tissue curvature has complicated a detailed analysis of its actomyosin networks. Here, we developed a computational workflow to create 2D apical shell reconstructions of the NE. Using these projections, we confirmed a midline-lateral gradient of apical cell area and discovered a negative correlated gradient of actomyosin density. We hypothesized that lateral neural folds, with high apical cell constriction and actomyosin, have higher apical tension than the midline hinge, with large apical cell area and low actomyosin. Through target laser ablations in live embryos that allow us to infer tension, we confirmed that tension is isotropic and low at the midline and anisotropic and high on the lateral neural folds. Finally, we identified sex differences in cell shape, apical constriction rates, actomyosin in the NE at an earlier time point than previously appreciated. We use these findings to propose a lateral tension mechanism used in murine NTC that is distinct from the contractile hinge mechanism identified in other model systems.