Affiliations: Business Unit Bioscience, Plant Research
International, Wageningen, The Netherlands | Human Genome Center, Institute of Medical Science,
University of Tokyo, Tokyo, Japan | BIOBASE GmbH, Wolfenbüttel, Germany
Abstract: We present a dynamical model of the gene network controlling flower
development in Arabidopsis thaliana. The network is centered at the
regulation of the floral organ identity genes (AP1, AP2, AP3,
PI and AG) and ends with the transcription factor complexes
responsible for differentiation of floral organs. We built and simulated the
regulatory interactions that determine organ specificity using an extension of
hybrid Petri nets as implemented in Cell Illustrator. The network
topology is characterized by two main features: (1) the presence of multiple
autoregulatory feedback loops requiring the formation of protein complexes, and
(2) the role of spatial regulators determining floral patterning. The resulting
network shows biologically coherent expression patterns for the involved genes,
and simulated mutants produce experimentally validated changes in organ
expression patterns. The requirement of heteromeric higher-order protein
complex formation for positive autoregulatory feedback loops attenuates
stochastic fluctuations in gene expression, enabling robust organ-specific gene
expression patterns. If autoregulation is mediated by monomers or homodimers of
proteins, small variations in initial protein levels can lead to biased
production of homeotic proteins, ultimately resulting in homeosis. We also
suggest regulatory feedback loops involving miRNA loci by which homeotic genes
control the activity of their spatial regulators.
