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Quantitative Analysis of Protein Expression to Study Lineage Specification in Mouse Preimplantation Embryos
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Published on: February 22, 2016

Predicting embryonic patterning using mutual entropy fitness and in silico evolution.

Paul François1, Eric D Siggia

  • 1Center for studies in Physics and Biology, The Rockefeller University, 1230 York Avenue, 10065 New York, NY, USA. pfrancois@rockefeller.edu

Development (Cambridge, England)
|June 24, 2010
PubMed
Summary

This study models Hox gene networks for embryonic anterior-posterior patterning. In silico evolution reveals how simple gene interactions, coordinated by a timer gene, can generate complex expression patterns during development.

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Area of Science:

  • Developmental biology
  • Evolutionary genetics
  • Systems biology

Background:

  • Vertebrate embryogenesis involves Hox genes for anterior-posterior (AP) axis formation.
  • Hox gene expression typically follows temporal colinearity and posterior prevalence rules.

Purpose of the Study:

  • Derive gene interaction networks for AP patterning using a fitness measure.
  • Investigate two developmental paradigms: patterning during growth and static morphogen gradients.
  • Model Hox gene regulation using simple activation and repression functions.

Main Methods:

  • Developed a mathematical measure for embryonic pattern quality (fitness).
  • Employed in silico evolution to evolve gene regulatory networks.
  • Simulated gene expression patterns under different developmental paradigms.

Main Results:

  • Derived networks mimicking Hox gene expression patterns, especially under a growth-paradigm.
  • Identified a 'timer gene' mechanism coordinating patterning with growth rate.
  • Demonstrated how a static morphogen gradient can arise from an ancestral system.

Conclusions:

  • In silico evolution quantitatively shows incremental evolution generating complex phenotypes.
  • Simple gene regulatory networks can explain complex Hox gene expression patterns.
  • A timer gene offers a parsimonious mechanism for coordinating development and growth.