On the origins of developmental robustness: Modeling buffering mechanisms against cell-level noise

During development, cells are subject to stochastic fluctuations in their positions (i.e. cell-level noise) which can potentially, lead to morphological noise (i.e., stochastic differences between morphologies that are expected to be equal, like the right and left sides of bilateral organisms). In this study we explore new and already existing hypotheses on buffering mechanisms against cell-level noise. Many of these hypotheses focus on how the boundaries between territories of gene expression remain regular and well-defined in spite of cell-level noise and division. We study these hypotheses and how irregular territory boundaries lead to morphological noise. To determine the consistency of the different hypotheses we use a general computational model of development, EmbryoMaker. EmbryoMaker can implement arbitrary gene networks regulating basic cell behaviors (contraction, adhesion, etc.), signaling and tissue biomechanics. We found that buffering mechanisms based on the orientation of cell divisions cannot lead to regular boundaries but that other buffering mechanisms can (homotypic adhesion, planar contraction, non-dividing boundaries, constant signaling and majority rule hypotheses). We also explored the effects of the shape and size of the territories on morphological noise.