Fine-grain patterns produced by juxtacrine signalling, have been studied using static monolayers as cellular domains. Unfortunately, analytical results are restricted to a few cells due to the algebraic complexity of nonlinear dynamical systems. Motivated by concentric patterning of Notch expression observed in the mammary gland, we combine concepts from graph and control theory to represent cellular connectivity. The resulting theoretical framework allows us to exploit the symmetry of multicellular bilayer structures in 2D and 3D, thereby deriving analytical conditions that drive the dynamical system to form laminar patterns consistent with the formulation of cell polarity. Critically, the conditions are independent of the precise dynamical details, thus the framework allows for the utmost generality in understanding the influence of cellular geometry on patterning in lateral-inhibition systems. Applying the analytic conditions to mammary organoids suggests that intense cell signalling polarity is required for the maintenance of stratified cell-types within a static bilayer using a lateral-inhibition mechanism. Furthermore, by employing 2D and 3D cell-based models, we highlight that the cellular polarity conditions derived from static domains have the capacity to generate laminar patterning in dynamic environments. However, they are insufficient for the maintenance of patterning when subjected to substantial morphological perturbations. In agreement with the mathematical implications of strict signalling polarity induced on the cells, we propose an adhesion dependent Notch-Delta biological process which has the potential to initiate bilayer stratification in a developing mammary organoid.
تحميل البحث