A quantitative data-driven model of cell proliferation and cell migration in the axolotl spinal cord regeneration.

CHARA OSVALDO

Gothenburg

Conferencia; 9th European Conference on Mathematical and Theoretical Biology; 2014

European Society for Mathematical and Theoretical Biology (ESMTB)

Unlike mammals and most other vertebrates, axolotl, the Mexican salamander (A. mexicanum) can regenerate entire limbs and even the spinal cord after their amputation. Hence, axolotl is a perfect model system for exploring regenerative mechanisms of the central nervous system of vertebrates. We quantified the density of neural progenitor cells and of mitotic events along the anteroposterior (AP) axis in axolotl spinal cord during the first 8 days of regeneration. These data  together with the analysis of cumulative BrdU labeling data allowed us to determine the time course of the cell cycle length of neural progenitor cells. In order to gain mechanistic understanding of the regenerative process we developed an ODE model of neural progenitor cell proliferation. The model loaded with the experimental time course of cell cycle length was not able to explain the experimentally observed cell numbers. In contrast, an alternative model involving both, proliferation and migration of cells towards the regenerating zone is able to reproduce the experimental data. Fitting  the model to the aforementioned experimental data allows us to predict a cell migratory velocity, the only free model parameter. Recently, we were able to perform cell tracking experiments to quantify migratory velocity of neural progenitor cells by electroporating axolotl larvae with a fluorescent reporter plasmid. The cell migratory velocity determined by this procedure confirms the prediction of our mathematical model.