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Published August 15, 2010 | Published
Journal Article Open

Perturbation analysis analyzed—mathematical modeling of intact and perturbed gene regulatory circuits for animal development

Abstract

Gene regulatory networks for animal development are the underlying mechanisms controlling cell fate specification and differentiation. The architecture of gene regulatory circuits determines their information processing properties and their developmental function. It is a major task to derive realistic network models from exceedingly advanced high throughput experimental data. Here we use mathematical modeling to study the dynamics of gene regulatory circuits to advance the ability to infer regulatory connections and logic function from experimental data. This study is guided by experimental methodologies that are commonly used to study gene regulatory networks that control cell fate specification. We study the effect of a perturbation of an input on the level of its downstream genes and compare between the cis-regulatory execution of OR and AND logics. Circuits that initiate gene activation and circuits that lock on the expression of genes are analyzed. The model improves our ability to analyze experimental data and construct from it the network topology. The model also illuminates information processing properties of gene regulatory circuits for animal development.

Additional Information

© 2010 Elsevier Inc. Received 27 January 2010; revised 29 March 2010; accepted 15 June 2010. Available online 20 June 2010. The author thanks Eric Davidson for insightful discussions and critical review of the manuscript. The author thanks Joel Smith, Dave McClay, Stefan Materna and Sagar Damle for critical review of the manuscript and helpful comments. The author thanks the two anonymous reviewers for their comments that helped to broaden the scope and the depth of the paper. Research was supported by NIH grant GM61005.

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