Modelling the Molecular Interactions in the Flower Developmental Network of Arabidopsis thaliana - Biological Petri Nets - page 279

Modelling the Molecular Interactions in the
Flower Developmental Network of
Arabidopsis thaliana

Kerstin Kaufmann a , Masao Nagasaki b and Ruy Jauregui c ,∗
a Business Unit Bioscience, Plant Research International, Wageningen, The Netherlands
b Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
c BIOBASE GmbH, Wolfenb uttel, 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.

KEYWORDS: Dynamical model, flower development, gene network

INTRODUCTION

Complex regulatory interactions between transcription factors and the prevalence of autoregulation are
common themes in gene regulatory networks. Recent evidence suggests that direct molecular interactions
form the basis of most regulatory processes: transcription factors generally bind a high number of sites
in the genome, and can thus potentially directly influence the expression of hundreds of genes [Farnham,
2009]. This paradigm may hold for all eukaryotes, since it is supported by data from animals (see, e.g.
Li et al. , 2008], and plants [e.g. Kaufmann et al. , 2009; Oh et al. , 2009].
Floral development is initiated in response to a variety of internal and environmental stimuli, such
as temperature and light (reviewed in Putterill

et al. , 2004). Different floral induction pathways are

∗ Corresponding author. E-mail: [e-mail] .