A multilayer network approach to polarity-driven cell-fate patterning in mammary organoids #

Joshua Moore

Poster session

Abstract #

Advances in high-resolution experimental methods have highlighted the significance of molecular pathway crosstalk in the development and disease of numerous mammalian biological systems. The investigation of multiple signal pathways often introduces different methods of cell-cell communication, i.e. paracrine and juxtacrine signalling. Motivated by concentric patterning of Notch1 expression observed in the mammary gland, we use multilayer-network coupled dynamical systems to describe discrete cellular interactions in bilayer tissues with mixed signalling mechanisms. Allowing for anisotropic network edge weights which represent cell signalling polarity, we analyse the interplay of tissue geometry, intracellular pathway crosstalk and signal polarity in the formation of laminar patterns in large-scale dynamical systems. We use methods of pattern templating by leveraging the symmetries within the topology of the cellular interaction structures, thereby deriving quotient systems that preserve the spatial information while allowing for an analytic approach to the emergence of patterns. Applying concepts from monotone dynamic systems, we then demonstrate the dominance of the templated pattern in the large-scale system by control of cell signal polarity. Critically, these methods of pattern analysis are independent of physical dimension and the number of cells in the tissue and therefore facilitate the study of pattern formation in tissues throughout their development. Applying our analytic methods to mammary organoids, we highlight that intense receptor/activator polarity is required for the robust convergence of laminar patterns of the Notch1 protein in an adhesion-dependent crosstalk system.