Organism-scale modeling of early Drosophila patterning via Bone Morphogenetic Proteins

摘要

Advances in image acquisition and informatics technology have led to organism-scale spatio-temporal atlases of gene expression and protein distributions. To maximize the utility of this information for the study of developmental processes, a new generation of mathematical models is needed for discovery and hypothesis testing. Here we develop a data-driven, geometrically-accurate, model of early Drosophila embryonic bone morphogenetic protein (BMP)-mediated patterning. We tested nine different mechanisms for signal transduction with feedback, eight combinations of geometry and gene expression prepatterns, and two scale-invariance mechanisms for their ability to reproduce proper BMP signaling output in wild-type and mutant embryos. We found that a model based on positive feedback of a secreted BMP binding protein, coupled with the experimentally-measured embryo geometry, provides the best agreement with population-mean image data. Our results demonstrate that using bioimages to build and optimize a 3D model provides significant new insights into mechanisms that guide tissue patterning.