Organogensis
VI.1 COORDINATORS
VI.2 PARTICIPANTS
VI.3 SUMMARY
VI.4 INTRODUCTION
VI.5 SPECIFIC AIMS
VI.6 BACKGROUND AND SIGNIFICANCE
VI.7 THEORETICAL FRAMEWORK
VI.8 PRELIMINARY RESULTS VI.9 RESEARCH DESIGN AND METHODS
VI.10 RELATIONSHIP TO CYTOSKELETON (PROJECT 2) AND BIOLOGICAL NETWORKS (PROJECT 1)
VI.11 TIMELINE
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VI.8.ii Theoretical and Computational Results:
Dr. Hentschel's laboratory has derived a set of partial PDEs based on the known biology of avian limb development, including FGFs and TGF- , capable of simulating chondrogenesis in vitro. They are now studying the conditions that may allow them to form the basis of a model for in vivo limb development. They have also investigated mechanisms involved in neurogenesis including bundling and guidance of axons, debundling and innervation of individual targets (Hentschel and van Ooyen, 1999).
Dr. Forgacs' laboratory has constructed a model which relates subcellular to supercellular viscoelastic properties (See Section VI.8.i). They have also constructed a model to describe pattern formation (beyond morphogenesis) involving the simultaneous motion of many cells and applied it to guide the successful experimental preparation of three-dimensional tube-like structures (primitive vasculature). They have modeled the entire evolution of a sea urchin embryo from first cleavage to the completion of gastrulation Forgacs and Drasdo, 2000; Forgacs et al., 1998).
Dr. Newman's laboratory has continued to elaborate an evolutionary biological framework to examine the role of physical determinants in development and their relation to genetic determinants (Salazar-Ciudad et al., 2001a, b). They have simulated the evolution of model pattern forming genetic networks and applied these results to the evolution of insect segmentation (Salazar-Ciudad et al., 2001a, b).
Dr. Alber's laboratory has used a cellular automaton to model the interaction between reaction-diffusion and cell-fibronectin adhesion in precartilage condensation formation, reproducing experimental results from Dr Newman's laboratory (Alber and Kiskowski, 2001; Kiskowski et al., 2002; Alber et al., 2002). They have developed cellular automaton models for the spatio-angular movement and interaction of two types of cells, which can choose their alignment and shown that cells separate to form confluent collections of cells of the same type moving in the same direction.
Dr. Glazier and Dr. Izaguirre's laboratories have designed and developed the CompuCell program which handles the CPM, reaction-diffusion and rule based cellular automata in an integrated fashion. The program allows flexible specification of parameters and visualization. CompuCell resembles Cello ( http://mbi.dkfz-heidelberg.de/mbi/research/cellsim/cello/index.html), developed independently at Deutsche Krebsforschungszentrum's (DKFZ, the German Cancer Research Center), Medical and Biological Informatics division. Like CompuCell, Cello achieves is generic and extensible, using Object Oriented software design. However, CompuCell integrates a mechanism for signaling by morphogen fields, which is not available in Cello. CompuCell's level of multi model integration is conceptually superior to Cello's.
Simulations using CompuCell have reproduced patterns of precursor morphogens (TGF- and fibronectin) and mesenchymal condensation resembling experiments in cartilaginous tissue. Section VI.9.i.d reproduces some simulation results. Binaries and simulation results are available from the link: http://www.nd.edu/~lcls.