A two-dimensional simulation model of the bicoid gradient in Drosophila.
BACKGROUND
Bicoid (Bcd) is a Drosophila morphogenetic protein responsible for patterning the anterior structures in embryos. Recent experimental studies have revealed important insights into the behavior of this morphogen gradient, making it necessary to develop a model that can recapitulate the biological features of the system, including its dynamic and scaling properties.


RESULTS
We present a biologically realistic 2-D model of the dynamics of the Bcd gradient in Drosophila embryos. This model is based on equilibrium binding of Bcd molecules to non-specific, low affinity DNA sites throughout the Drosophila genome. It considers both the diffusion media within which the Bcd gradient is formed and the dynamic and other relevant properties of bcd mRNA from which Bcd protein is produced. Our model recapitulates key features of the Bcd protein gradient observed experimentally, including its scaling properties and the stability of its nuclear concentrations during development. Our simulation model also allows us to evaluate the effects of other biological activities on Bcd gradient formation, including the dynamic redistribution of bcd mRNA in early embryos. Our simulation results suggest that, in our model, Bcd protein diffusion is important for the formation of an exponential gradient in embryos.


CONCLUSIONS
The 2-D model described in this report is a simple and versatile simulation procedure, providing a quantitative evaluation of the Bcd gradient system. Our results suggest an important role of Bcd binding to non-specific, low-affinity DNA sites in proper formation of the Bcd gradient in our model. They demonstrate that highly complex biological systems can be effectively modeled with relatively few parameters.
Deng
Jingyuan
J
Division of Biomedical Informatics, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio, United States of America.
Wang
Wei
W
Lu
Long Jason
LJ
Ma
Jun
J
D000818:Animals; D001665:Binding Sites; D019521:Body Patterning; D003198:Computer Simulation; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins; D004058:Diffusion; D004330:Drosophila; D029721:Drosophila Proteins; D004625:Embryo, Nonmammalian; D049750:Genome, Insect; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D009024:Morphogenesis; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; C056478:bcd protein, Drosophila; D004247:DNA