Multi-model Simulations of Chicken Limb Morphogenesis

Early development of multicellular organisms (morphogenesis) is a complex phenomenon. We present COMPUCELL, a multi-model software framework for simulations of morphogenesis. As an example, we simulate the formation of the skeletal pattern in the avian limb bud, which requires simulations based on interactions of the genetic regulatory network with generic cellular mechanisms (cell adhesion, haptotaxis, and chemotaxis). A combination of a rule-based state automaton and sets of differential equations, both subcellular ordinary differential equations (ODEs) and domain-level reaction-diffusion partial differential equations (PDEs) models genetic regulation. This regulation controls the differentiation of cells, and also cell-cell and cell-extracellular matrix interactions that give rise to cell pattern formation and cell rearrangements such as mesenchymal condensation. The cellular Potts model (CPM) models cell dynamics (cell movement and rearrangement). These models couple; COMPUCELL provides an integrated framework for such computations. Binaries for Microsoft Windows and Solaris are available. Source code is available on request, via email: compucell@cse.nd.edu.