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10:41
Generation of Dispersed Presomitic Mesoderm Cell Cultures for Imaging of the Zebrafish Segmentation Clock in Single Cells
Published on: July 24, 2014
Somitogenesis clock-wave initiation requires differential decay and multiple binding sites for clock protein
Mark Campanelli1, Tomás Gedeon
1Department of Mathematics and Computer Science, Southwest Minnesota State University, Marshall, Minnesota, United States of America.
Plos Computational Biology
|April 7, 2010
Summary
Somitogenesis relies on gene expression waves originating from the presomitic mesoderm. A mathematical model reveals that multiple binding sites and differential decay rates are crucial for forming these essential developmental waves.
Area of Science:
- Developmental biology
- Systems biology
- Mathematical modeling
Background:
- Somitogenesis is a fundamental process in vertebrate embryonic development, forming segmented blocks of cells (somites) from the presomitic mesoderm (PSM).
- Somite formation is driven by periodic gene expression waves originating in the tailbud and propagating across the PSM.
- Previous hypotheses suggest a spatiotemporally graded control protein influences the oscillation rate of clock-gene expression.
Purpose of the Study:
- To investigate the contribution of two key control mechanisms to the initial formation of gene-expression waves during somitogenesis.
- To test biologically motivated model scenarios exploring the roles of transcription binding sites and protein decay rates.
Main Methods:
- Development of a minimally constructed mathematical model of gene-expression dynamics.
- Simulation of four distinct model scenarios incorporating variations in transcription binding sites (one or two) and clock protein decay rates (differential or not).
- Analysis of wave formation sensitivity to model parameters and robustness to cellular heterogeneity.
Main Results:
- Only a model incorporating both multiple transcription binding sites and differential decay rates for clock protein monomers and dimers successfully reproduced experimentally observed waveforms.
- Sensitivity analyses revealed critical parameter dependencies for wave formation.
- The model demonstrated robustness to heterogeneity within the cell population.
Conclusions:
- The study identifies specific genetic control mechanisms underlying the initiation of somitogenesis waves.
- Experimental observations of somitogenesis wave initiation provide strong constraints on the molecular mechanisms involved.
- A model with multiple binding sites and differential decay rates is essential for accurately simulating developmental gene expression patterns.
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