Organism-scale modeling of early Drosophila patterning via bone morphogenetic proteins.
Advances in image acquisition and informatics technology have led to organism-scale spatiotemporal 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 three-dimensional model provides significant insights into mechanisms that guide tissue patterning.
Agricultural and Biological Engineering, Weldon School of Biomedical Engineering, and Bindley Bioscience Center, 225 South University Street, Purdue University, West Lafayette, IN 47907, USA.
David M
DM
Umulis
Osamu
O
Shimmi
Michael B
MB
O'Connor
Hans G
HG
Othmer
D000818:Animals; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000502:physiology*; D024141:Collagen Type IV / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics / Q000502:physiology*; D025461:Feedback, Physiological; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D021621:Imaging, Three-Dimensional; D008954:Models, Biological; D009154:Mutation; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
D019485:Bone Morphogenetic Proteins; D024141:Collagen Type IV; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C112506:MAD protein, Drosophila; D014157:Transcription Factors