Embryonic geometry underlies phenotypic variation in decanalized conditions

During development, many mutations cause increased variation in phenotypic outcomes, a phenomenon termed decanalization. Such variations can often be attributed to genetic and environmental perturbations. However, phenotypic discordance remains even in isogenic model organisms raised in homogeneous environments. To understand the mechanisms underlying phenotypic variation, we used as a model the highly precise anterior-posterior (AP) patterning of the early Drosophila embryo. We decanalized the system by depleting the maternal bcd product and found that in contrast to the highly scaled patterning in the wild-type, the segmentation gene boundaries shift away from the scaled positions according to the total embryonic length. Embryonic geometry is hence a key factor predetermining patterning outcomes in such decanalized conditions. Embryonic geometry was also found to predict individual patterning outcomes under bcd overexpression, another decanalizing condition. Further analysis of the gene regulatory network acting downstream of the morphogen identified vulnerable points in the networks due to limitations in the available physical space.