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.
Umulis
David M
DM
Agricultural and Biological Engineering, Weldon School of Biomedical Engineering, and Bindley Bioscience Center, 225 South University Street, Purdue University, West Lafayette, IN 47907, USA.
Shimmi
Osamu
O
O'Connor
Michael B
MB
Othmer
Hans G
HG
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