a boolean model of the cardiac gene regulatory network determining first and second heart field identity一个布尔的心脏基因调控网络模型确定第一和第二心脏领域的身份.pdfVIP

A Boolean Model of the Cardiac Gene Regulatory Network Determining First and Second Heart Field Identity 1,2,3. 1,3. 1 1 ¨ 2 Franziska Herrmann , Alexander Groß , Dao Zhou , Hans A. Kestler *, Michael Kuhl * 1 Research Group Bioinformatics and Systems Biology, Institute for Neural Information Processing, Ulm University, Ulm, Germany, 2 Institute for Biochemistry and Molecular Biology, Ulm University, Ulm, Germany, 3 International Graduate School in Molecular Medicine, Ulm University, Ulm, Germany Abstract Two types of distinct cardiac progenitor cell populations can be identified during early heart development: the first heart field (FHF) and second heart field (SHF) lineage that later form the mature heart. They can be characterized by differential expression of transcription and signaling factors. These regulatory factors influence each other forming a gene regulatory network. Here, we present a core gene regulatory network for early cardiac development based on published temporal and spatial expression data of genes and their interactions. This gene regulatory network was implemented in a Boolean computational model. Simulations reveal stable states within the network model, which correspond to the regulatory states of the FHF and the SHF lineages. Furthermore, we are able to reproduce the expected temporal expression patterns of early cardiac factors mimicking developmental progression. Additionally, simulations of knock-down experiments within our model resemble published phenotypes of mutant mice. Consequently, this gene regulatory network retraces the early steps and requirements of cardiogenic mesoderm determination in a way appropriate to enhance the understanding of heart