Modeling of multicellular feedback loops in plant stem cells
Stem cells are crucial to growth and architecture of plants. Our group has discovered a major gene regulatory network involved in the positioning and outgrowth of all stem cell groups from plant embryogenesis to root, shoot and flower formation. (1-4). A key aspect of the network is the presence of multiple feedback loops wired in topologies that we refer to as ‘regulatory knots’.
Our microarray and ChIP data reveal that the PLETHORA transcription factors are key hubs in these regulatory knots. We have first modeled signal flow in this network using Cellular Potts modeling (5). More recently, we have linked gene regulatory networks encoded in PDEs to static and growing grid-based cell and tissue models. These modeling efforts are beginning to reveal principles of self-organization in multicellular systems (Dhonuskhe et al., Cruz-Ramirez et al., manuscripts in review). Finally, we have started bottom-up models that explore minimal principles of self-organization which explain pattern formation from initial perturbations of a regulatory network present in all cells.
Bottom-up and top-down models
In the proposed project, we like to take our modeling efforts one step further. The bottom-up models now need to be connected to the specific information emanating from experimental manipulation of the PLT network and the information from the top-down networks that explain some regulatory circuits. For that purpose, different modeling platforms will be combined or emulated in a system that can meaningfully implement the outcome of lower-level models (i.e., gene regulatory networks, cytoskeleton arrangements) into higher level models. The ultimate goal is to simulate the generation of plant architecture from biologically relevant rules that can be tested by experiment. For our project, we will continue our current collaborations in Wageningen (Bela Mulder), Utrecht (Rob de Boer) and Norwich (Stan Maree and Veronica Grieneisen).