Towards in Silico Organogenesis: Inferring and Simulating Regulatory Network Dynamics on Growing Embryonic 3D Limb Bud Domains

Limb bud development is a paradigm to study organogenesis. Through extensive experimental studies, data has been gathered on the growing embryonic limb bud. Signalling centres that instruct cells as to their purpose and proliferation have been identified. In addition, the major network components and their regulatory interactions have also been established. The objective is to use the high quality data sets to build a realistic computational model of the developing limb bud on 3D growing, embryonic domains that contain gene expression information. This will require using and improving available numerical methods and developing approaches for image-based parameter estimation. 

Currently, we are developing a 2D data-based spatio-temporal computational model of limb development, formulated as a coupled system of non-linear partial differential equations (PDEs). This can address key issues of limb bud development and explain the behaviour, including alterations in gene expression level and localization, of various mutants.

As a next step, modeling growing 3-D limb bud geometries will enable addressing the specific gene expression patterns in a more reliable way, which was limited on 2-D simulations. Additionally, implementation of parameter estimation methods will enable testing the gene regulatory network more vigorously.

Mot-clé: Mathematical modeling, limb bud development, organogenesis, signaling networks, numerical methods, parameter estimation