Canalization of gene expression in the Drosophila blastoderm by gap gene cross regulation

Developing embryos exhibit a robust capability to reduce phenotypic variations that occur naturally or as a result of experimental manipulation. This reduction in variation occurs by an epigenetic mechanism called canalization, a phenomenon which has resisted understanding because of a lack of neces...

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Bibliographic Details
Published in:PLoS biology 2009-03, Vol.7 (3), p.e1000049-e1000049
Main Authors: Manu, Surkova, Svetlana, Spirov, Alexander V, Gursky, Vitaly V, Janssens, Hilde, Kim, Ah-Ram, Radulescu, Ovidiu, Vanario-Alonso, Carlos E, Sharp, David H, Samsonova, Maria, Reinitz, John
Format: Article
Language:English
Subjects:
Animals
BASIC BIOLOGICAL SCIENCES
Biophysics
Blastoderm - embryology
Blastoderm - metabolism
Body Patterning - genetics
Computational Biology
Developmental Biology
Drosophila
drosophila melanogaster
Drosophila melanogaster - embryology
Drosophila melanogaster - genetics
Drosophila Proteins - deficiency
Drosophila Proteins - genetics
eggs
embryonic pattern formation
embryos
Environment
Epigenesis, Genetic
Evolutionary Biology
Gene expression
Gene Expression Regulation, Developmental
gene regulation
Genetic engineering
Genetic Variation
Genetics and Genomics
GTPase-Activating Proteins - genetics
GTPase-Activating Proteins - metabolism
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Insects
Kruppel-Like Transcription Factors - deficiency
Kruppel-Like Transcription Factors - genetics
Mathematical models
Mathematics
Models, Theoretical
morphogenic segmentation
Repressor Proteins - deficiency
Repressor Proteins - genetics
Studies
synthetic genetic network
Trans-Activators - genetics
Trans-Activators - metabolism
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Summary:Developing embryos exhibit a robust capability to reduce phenotypic variations that occur naturally or as a result of experimental manipulation. This reduction in variation occurs by an epigenetic mechanism called canalization, a phenomenon which has resisted understanding because of a lack of necessary molecular data and of appropriate gene regulation models. In recent years, quantitative gene expression data have become available for the segment determination process in the Drosophila blastoderm, revealing a specific instance of canalization. These data show that the variation of the zygotic segmentation gene expression patterns is markedly reduced compared to earlier levels by the time gastrulation begins, and this variation is significantly lower than the variation of the maternal protein gradient Bicoid. We used a predictive dynamical model of gene regulation to study the effect of Bicoid variation on the downstream gap genes. The model correctly predicts the reduced variation of the gap gene expression patterns and allows the characterization of the canalizing mechanism. We show that the canalization is the result of specific regulatory interactions among the zygotic gap genes. We demonstrate the validity of this explanation by showing that variation is increased in embryos mutant for two gap genes, Krüppel and knirps, disproving competing proposals that canalization is due to an undiscovered morphogen, or that it does not take place at all. In an accompanying article in PLoS Computational Biology (doi:10.1371/journal.pcbi.1000303), we show that cross regulation between the gap genes causes their expression to approach dynamical attractors, reducing initial variation and providing a robust output. These results demonstrate that the Bicoid gradient is not sufficient to produce gap gene borders having the low variance observed, and instead this low variance is generated by gap gene cross regulation. More generally, we show that the complex multigenic phenomenon of canalization can be understood at a quantitative and predictive level by the application of a precise dynamical model.
ISSN:1545-7885
1544-9173
1545-7885
DOI:10.1371/journal.pbio.1000049