Embryonic geometry underlies phenotypic variation in decanalized conditions.

During development, many mutations cause increased variation in phenotypic outcomes, a phenomenon termed decanalization. Phenotypic discordance is often observed in the absence of genetic and environmental variations, but the mechanisms underlying such inter-individual phenotypic discordance remain elusive. Here, using the anterior-posterior (AP) patterning of the embryo, we identified embryonic geometry as a key factor predetermining patterning outcomes under decanalizing mutations. With the wild-type AP patterning network, we found that AP patterning is robust to variations in embryonic geometry; segmentation gene expression remains reproducible even when the embryo aspect ratio is artificially reduced by more than twofold. In contrast, embryonic geometry is highly predictive of individual patterning defects under decanalized conditions of either increased dosage or knockout. We showed that the phenotypic discordance can be traced back to variations in the gap gene expression, which is rendered sensitive to the geometry of the embryo under mutations.