Modeling study of the impact of actomyosin contractility on cell proliferation in the Drosophila wing imaginal disc.

Abstract

A fundamental open question in developmental biology is deciphering how the regulation of cell proliferation and the actomyosin cytoskeleton coordinate proper formation and maintenance of tissue shape and size. To address this question, a close integration between experimental work and simulations from a novel multi-scale computational model are used. Specifically, a subcellular element (SCE) model of the Drosophila wing imaginal disc cross-section along the anterior-posterior axis is developed and calibrated using experimental data. This model accounts for actomyosin contractility in different cell regions and incorporates a detailed cell division sub model capable of capturing interkinetic nuclear migration, a fundamental process for proper cell division. Coupled model simulations and experiments reveal that anisotropic patterning of actomyosin contractility can regulate basal local curvature of the wing disc and positioning of nuclei. Moreover, it was found that cell proliferation also plays an important role in regulating basal curvature. However, this model has a simplified representation of actomyosin contractility which is not able to capture the micro level interactions between actin filaments and myosin motors that make up the actomyosin network and thus, the direction of the contractile forces cannot be accounted for explicitly. Therefore, in order to have a more biological representation of actomyosin, a coarse-grained stochastic model of subcellular level actomyosin network dynamics in two-dimensions is being developed. This model describes the actomyosin network via a large system of nodes with their dynamics represented by stochastic ordinary differential equations. The multi-scale SCE model, coupled with the stochastic model, will be used to gain insight into the detailed mechanism of how actomyosin contractility facilitates interkinetic nuclear migration, cell proliferation and formation of the wing shape.