Axolotl spinal cord regeneration: a data-driven mathematical model

CURA COSTA, EMANUEL; CHARA, OSVALDO

Buenos Aires

Taller; A systems approach to biology; 2018

FCEyN, UBA

The axolotl (Ambystoma mexicanum) completely regenerates the spinal cord after tail amputation. We demonstrated that this regenerative process is mainly driven by an acceleration of the cell cycle of resident neural stem cells (Rost et al., 2016) while re-establishing planar cell polarity (PCP) signaling (Rodrigo Albors et al., 2015). We previously quantified a particular spatiotemporal distribution of mitoses along the axolotl spinal cord during regeneration (Rost et al., 2016). What determines this mitoses distribution remains yet to be elucidated and it constitutes the subject of the present study. We developed a data-driven mathematical model of the axolotl spinal cord during regeneration. We implemented a Cellular Potts Model (CPM) describing the dynamics of neural stem cells in terms of a division probability linked to our previously quantified mitotic index along the axolotl spinal cord during regeneration (Rost et al., 2016). The model successfully reproduced experimental data of axolotl spinal cord outgrowth. We are now studying whether the spatiotemporal distribution of mitoses can be triggered by a putative and yet unknown signal. To do that, we proposed a multi-scale model incorporating a signal under a reaction-diffusion scheme as a second layer of the neural cell layer. We will show preliminary simulations evaluating possible roles of the signal on the axolotl spinal cord outgrowth dynamics.References: Rodrigo Albors A, Tazaki A, Rost F, Nowoshilow S, Chara O & Tanaka EM. 2015. eLife. 4:e10230. Rost F, Rodrigo Albors A, Mazurov V, Brusch L, Deutsch A, Tanaka EM & Chara O. 2016. eLife. 5:e20357