Dynamics of PAR proteins explain the oscillation and ratcheting mechanisms in dorsal closure

Abstract

We present a vertex-based model for Drosophila dorsal closure that predicts the mechanics of cell oscillation and contraction from the dynamics of the PAR proteins. Based on experimental observations of how aPKC, Par-6 and Bazooka migrate from the circumference of the apical surface to the medial domain, and how they interact with each other and ultimately regulate the apicomedial actomyosin, we formulate a system of differential equations that capture the key features of the process. The oscillation in cell area in the early phase of dorsal closure results from an intracellular negative feedback loop that involves myosin, an actomyosin regulator, aPKC and Bazooka. In the slow phase, gradual sequestration of apicomedial aPKC into Bazooka clusters causes incomplete disassembly of the myosin network over each cycle of oscillation, thus producing the so-called ratchet. The fast phase of rapid cell and tissue contraction arises when medial myosin, no longer hindered by aPKC, builds up in time and produces sustained contraction. Thus, a minimal set of rules governing the dynamics of the PAR proteins, extracted from experimental observations, can account for all major mechanical outcomes of dorsal closure, including the transitions between its three distinct phases.\n\nInsert Received for publication Date and in final form Date