Organism-Scale Modeling of Early Drosophila Patterning via Bone Morphogenetic Proteins

• Published in: Developmental cell 2010-02, Vol.18 (2), p.260-274
• Main Authors: Umulis, David M., Shimmi, Osamu, O'Connor, Michael B., Othmer, Hans G.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Body Patterning - genetics; Body Patterning - physiology; Bone Morphogenetic Proteins - genetics; Bone Morphogenetic Proteins - physiology; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Collagen Type IV - genetics; Collagen Type IV - physiology; DEVBIO; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Drosophila; Drosophila melanogaster - embryology; Drosophila melanogaster - genetics; Drosophila melanogaster - physiology; Drosophila Proteins - genetics; Drosophila Proteins - physiology; Feedback, Physiological; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental; Genes, Insect; Imaging, Three-Dimensional; Models, Biological; Molecular and cellular biology; Mutation; Signal Transduction; SIGNALING; SYSBIO; Transcription Factors - genetics; Transcription Factors - physiology
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2010.01.006

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. [Display omitted] ► Capturing 3D spatiotemporal content of expression data increases model utility ► Embryo geometry shapes signaling; prepatterns compensate in misshapen embryos ► Cell-surface binding proteins compensate for weak ligand/inhibitor/receptor binding ► BMP-mediated patterning is “nearly” scale-invariant