Deutsche Forschungsgemeinschaft – Center for Regenerative Therapies Dresden, Dresden, Germany; Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
Vladimir Mazurov
Deutsche Forschungsgemeinschaft – Center for Regenerative Therapies Dresden, Dresden, Germany; Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
Lutz Brusch
Center for Information Services and High Performance Computing, Technische Universität Dresden, Dresden, Germany; Center for Advancing Electronics Dresden, Dresden, Germany
Andreas Deutsch
Center for Information Services and High Performance Computing, Technische Universität Dresden, Dresden, Germany; Center for Advancing Electronics Dresden, Dresden, Germany
Elly M Tanaka
Deutsche Forschungsgemeinschaft – Center for Regenerative Therapies Dresden, Dresden, Germany; Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
Center for Information Services and High Performance Computing, Technische Universität Dresden, Dresden, Germany; Systems Biology Group, Institute of Physics of Liquids and Biological Systems, National Scientific and Technical Research Council, University of La Plata, La Plata, Argentina
Axolotls are unique in their ability to regenerate the spinal cord. However, the mechanisms that underlie this phenomenon remain poorly understood. Previously, we showed that regenerating stem cells in the axolotl spinal cord revert to a molecular state resembling embryonic neuroepithelial cells and functionally acquire rapid proliferative divisions (Rodrigo Albors et al., 2015). Here, we refine the analysis of cell proliferation in space and time and identify a high-proliferation zone in the regenerating spinal cord that shifts posteriorly over time. By tracking sparsely-labeled cells, we also quantify cell influx into the regenerate. Taking a mathematical modeling approach, we integrate these quantitative datasets of cell proliferation, neural stem cell activation and cell influx, to predict regenerative tissue outgrowth. Our model shows that while cell influx and neural stem cell activation play a minor role, the acceleration of the cell cycle is the major driver of regenerative spinal cord outgrowth in axolotls.
