Algebraic framework for determining laminar pattern bifurcations by lateral-inhibition in 2D and 3D bilayer geometries

TL;DR

This paper develops an algebraic framework using graph and control theory to analyze how cellular geometry influences laminar pattern formation in lateral-inhibition systems within 2D and 3D bilayer structures, with applications to mammary gland organoids.

Contribution

It introduces a general analytical approach that leverages symmetry in multicellular bilayers to determine patterning conditions independent of specific dynamics.

Findings

Cell polarity is crucial for maintaining stratified cell types in bilayers.

Static domain conditions can induce laminar patterns in dynamic models.

Patterning stability is challenged by significant morphological changes.

Abstract

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.