Analysis of Gap Gene Reguation in a 3D Organism-Scale Model of the Drosophila melanogaster Embryo
The axial bodyplan of Drosophila melanogaster is determined during a process
called morphogenesis. Shortly after fertilization, maternal bicoid mRNA is
translated into Bicoid (Bcd). This protein establishes a spatially graded
morphogen distribution along the anterior-posterior (AP) axis of the embryo.
Bcd initiates AP axis determination by triggering expression of gap genes that
subsequently regulate each other's expression to form a precisely controlled
spatial distribution of gene products. Reaction-diffusion models of gap gene
expression on a 1D domain have previously been used to infer complex genetic
regulatory network (GRN) interactions by optimizing model parameters with
respect to 1D gap gene expression data. Here we construct a finite element
reaction-diffusion model with a realistic 3D geometry fit to full 3D gap gene
expression data. Though gap gene products exhibit dorsal-ventral asymmetries,
we discover that previously inferred gap GRNs yield qualitatively correct AP
distributions on the 3D domain only when DV-symmetric initial conditions are
employed. Model patterning loses qualitative agreement with experimental data
when we incorporate a realistic DV-asymmetric distribution of Bcd. Further, we
find that geometry alone is insufficient to account for DV-asymmetries in the
final gap gene distribution. Additional GRN optimization confirms that the 3D
model remains sensitive to GRN parameter perturbations. Finally, we find that
incorporation of 3D data in simulation and optimization does not constrain the
search space or improve optimization results.
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Text Reference
James Hengenius, Michael Gribskov, Ann Rundell, Charless Fowlkes, and David Umulis. Analysis of gap gene reguation in a 3d organism-scale model of the drosophila melanogaster embryo. PLoS ONE, 6:e26797, 2011.BibTeX Reference
@article{Hengenius_PLOS1_2011,AUTHOR = "Hengenius, James and Gribskov, Michael and Rundell, Ann and Fowlkes, Charless and Umulis, David",
TITLE = "Analysis of Gap Gene Reguation in a 3D Organism-Scale Model of the Drosophila melanogaster Embryo",
Journal = "PLoS ONE",
Year = "2011",
Volume = "6",
Issue = "11",
pages = "e26797",
TAG = "biological_images"
}