Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 9, Pages 3213-3218Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0810728106
Keywords
computational modeling; Drosophila; signaling; systems biology
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Funding
- National Institutes of Health [P50 GM071508, R01 GM078079]
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Systematic validation of pattern formation mechanisms revealed by molecular studies of development is essentially impossible without mathematical models. Models can provide a compact summary of a large number of experiments that led to mechanism formulation and guide future studies of pattern formation. Here, we realize this program by analyzing a mathematical model of epithelial patterning by the highly conserved EGFR and BMP signaling pathways in Drosophila oogenesis. The model accounts for the dynamic interaction of the feedforward and feedback network motifs that control the expression of Broad, a zinc finger transcription factor expressed in the cells that form the upper part of the respiratory eggshell appendages. Based on the combination of computational analysis and genetic experiments, we show that the model accounts for the key features of wild-type pattern formation, correctly predicts patterning defects in multiple mutants, and guides the identification of additional regulatory links in a complex pattern formation mechanism.
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