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

ABSTRACT

During development, cells are subject to stochastic fluctuations in their positions (i.e. cell-level noise) that can potentially lead to morphological noise (i.e. stochastic differences between morphologies that are expected to be equal, e.g. the right and left sides of bilateral organisms). In this study, we explore new and 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, despite 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 explore the effects of the shape and size of the territories on morphological noise.