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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1110-1118
Number of pages9
JournalDevelopmental Biology
Volume344
Issue number2
DOIs
StatePublished - Aug 2010
Externally publishedYes

Bibliographical note

Funding Information:
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 .

Keywords

  • Gene regulatory networks
  • Mathematical modeling
  • Perturbation analysis

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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