title: Accelerated cell divisions drive the outgrowth of the regenerating spinal cord in axolotls.
abstract: 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.
authors.affiliation: Center for Information Services and High Performance Computing, Technische Universität Dresden, Dresden, Germany.
authors.forename: Fabian
authors.identifier: http://orcid.org/0000-0001-6466-2589
authors.initials: F
authors.lastname: Rost
authors.affiliation: Deutsche Forschungsgemeinschaft - Center for Regenerative Therapies Dresden, Dresden, Germany.|Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
authors.forename: Aida
authors.identifier: http://orcid.org/0000-0002-9573-2639
authors.initials: A
authors.lastname: Rodrigo Albors
authors.affiliation: Deutsche Forschungsgemeinschaft - Center for Regenerative Therapies Dresden, Dresden, Germany.|Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Mazurov
authors.affiliation: Center for Information Services and High Performance Computing, Technische Universität Dresden, Dresden, Germany.|Center for Advancing Electronics Dresden, Dresden, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Brusch
authors.affiliation: Center for Information Services and High Performance Computing, Technische Universität Dresden, Dresden, Germany.|Center for Advancing Electronics Dresden, Dresden, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Deutsch
authors.affiliation: Deutsche Forschungsgemeinschaft - Center for Regenerative Therapies Dresden, Dresden, Germany.|Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
authors.forename: Elly M
authors.initials: EM
authors.lastname: Tanaka
authors.affiliation: 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.
authors.forename: Osvaldo
authors.identifier: http://orcid.org/0000-0002-0868-2507
authors.initials: O
authors.lastname: Chara
mesh_terms: D000558:Ambystoma mexicanum; D000818:Animals; D049109:Cell Proliferation; D008962:Models, Theoretical; D058953:Neural Stem Cells / Q000502:physiology*; D062211:Spatio-Temporal Analysis; D058630:Spinal Cord Regeneration
keywords: axolotl; cell proliferation; computational biology; developmental biology; modeling; regeneration; stem cells; systems biology