Lembong Jessica, Yakoby Nir, Shvartsman Stanislav Y
Department of Chemical Engineering and Lewis-Sigler Institute for Integrative Genomics, Washington Road, Princeton University, Princeton, NJ 08544, USA.
Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3213-8. doi: 10.1073/pnas.0810728106. Epub 2009 Feb 13.
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.
如果没有数学模型，对发育分子研究揭示的模式形成机制进行系统验证基本上是不可能的。模型可以对大量导致机制形成的实验进行简洁总结，并指导未来的模式形成研究。在这里，我们通过分析果蝇卵子发生过程中高度保守的表皮生长因子受体（EGFR）和骨形态发生蛋白（BMP）信号通路的上皮模式数学模型来实现这个计划。该模型解释了前馈和反馈网络基序的动态相互作用，这些基序控制着Broad的表达，Broad是一种锌指转录因子，在形成呼吸性卵壳附属物上部的细胞中表达。基于计算分析和基因实验的结合，我们表明该模型解释了野生型模式形成的关键特征，正确预测了多个突变体中的模式形成缺陷，并指导了在复杂模式形成机制中识别其他调控联系。
