The in Silico Limb: Building a Dynamic Spatial Model for Morpho-regulatory Signaling Interactions During Vertebrate Organogenesis

Vertebrate limb development is an excellent model to study how complex genetic networks regulate vertebrate organogenesis and tissue development. Decades of experimental studies have led to the identification of all major network components and their regulatory interactions. Furthermore signaling centers have been identified that instruct cells in an embryonic field with respect to their particular fates and proliferation potential. In spite of much detailed knowledge, an integrative understanding is still lacking.

We therefore seek to develop a data-based spatio-temporal computational model of limb development, formulated as a coupled system of non-linear partial differential equations (PDEs). To that end we use Optical Projection Tomography (OPT) to acquire 3-D images of the gene expression patterns at different stages of the mouse embryonic development and FACS analysis to count cell populations. 

The integrative understanding of the dynamics and spatial control of signaling interactions will be of likely relevance to the directed engineering of tissues from stem cells and for regenerative medicine.

Mot-clé: Vertebrate Limb Development, Mathematical Modeling, 3-D Imaging