Spatiotemporal control of cell cycle acceleration during axolotl spinal cord regeneration

Axolotls are uniquely able to resolve spinal cord injuries, but little is known about the mechanisms underlying spinal cord regeneration. We previously found that tail amputation leads to reactivation of a developmental-like program in spinal cord ependymal cells (Rodrigo Albors et al., 2015), chara...

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Main Authors: Emanuel Cura Costa, Leo Otsuki, Aida Rodrigo Albors, Elly M Tanaka, Osvaldo Chara
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2021-05-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/55665
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author Emanuel Cura Costa
Leo Otsuki
Aida Rodrigo Albors
Elly M Tanaka
Osvaldo Chara
author_facet Emanuel Cura Costa
Leo Otsuki
Aida Rodrigo Albors
Elly M Tanaka
Osvaldo Chara
author_sort Emanuel Cura Costa
collection DOAJ
description Axolotls are uniquely able to resolve spinal cord injuries, but little is known about the mechanisms underlying spinal cord regeneration. We previously found that tail amputation leads to reactivation of a developmental-like program in spinal cord ependymal cells (Rodrigo Albors et al., 2015), characterized by a high-proliferation zone emerging 4 days post-amputation (Rost et al., 2016). What underlies this spatiotemporal pattern of cell proliferation, however, remained unknown. Here, we use modeling, tightly linked to experimental data, to demonstrate that this regenerative response is consistent with a signal that recruits ependymal cells during ~85 hours after amputation within ~830 μm of the injury. We adapted Fluorescent Ubiquitination-based Cell Cycle Indicator (FUCCI) technology to axolotls (AxFUCCI) to visualize cell cycles in vivo. AxFUCCI axolotls confirmed the predicted appearance time and size of the injury-induced recruitment zone and revealed cell cycle synchrony between ependymal cells. Our modeling and imaging move us closer to understanding bona fide spinal cord regeneration.
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spelling doaj.art-b1a93a44e4b346c1b6fe4dbbf2189ca12022-12-22T03:38:04ZengeLife Sciences Publications LtdeLife2050-084X2021-05-011010.7554/eLife.55665Spatiotemporal control of cell cycle acceleration during axolotl spinal cord regenerationEmanuel Cura Costa0https://orcid.org/0000-0002-7030-2077Leo Otsuki1https://orcid.org/0000-0001-6107-2508Aida Rodrigo Albors2https://orcid.org/0000-0002-9573-2639Elly M Tanaka3https://orcid.org/0000-0003-4240-2158Osvaldo Chara4https://orcid.org/0000-0002-0868-2507Systems Biology Group (SysBio), Institute of Physics of Liquids and Biological Systems (IFLySIB), National Scientific and Technical Research Council (CONICET) and University of La Plata (UNLP), La Plata, ArgentinaThe Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, AustriaDivision of Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dundee, United KingdomThe Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, AustriaSystems Biology Group (SysBio), Institute of Physics of Liquids and Biological Systems (IFLySIB), National Scientific and Technical Research Council (CONICET) and University of La Plata (UNLP), La Plata, Argentina; Center for Information Services and High Performance Computing, Technische Universität Dresden, Dresden, GermanyAxolotls are uniquely able to resolve spinal cord injuries, but little is known about the mechanisms underlying spinal cord regeneration. We previously found that tail amputation leads to reactivation of a developmental-like program in spinal cord ependymal cells (Rodrigo Albors et al., 2015), characterized by a high-proliferation zone emerging 4 days post-amputation (Rost et al., 2016). What underlies this spatiotemporal pattern of cell proliferation, however, remained unknown. Here, we use modeling, tightly linked to experimental data, to demonstrate that this regenerative response is consistent with a signal that recruits ependymal cells during ~85 hours after amputation within ~830 μm of the injury. We adapted Fluorescent Ubiquitination-based Cell Cycle Indicator (FUCCI) technology to axolotls (AxFUCCI) to visualize cell cycles in vivo. AxFUCCI axolotls confirmed the predicted appearance time and size of the injury-induced recruitment zone and revealed cell cycle synchrony between ependymal cells. Our modeling and imaging move us closer to understanding bona fide spinal cord regeneration.https://elifesciences.org/articles/55665axolotlspinal cord regenerationcomputational modelcell proliferationFUCCIcell cycle
spellingShingle Emanuel Cura Costa
Leo Otsuki
Aida Rodrigo Albors
Elly M Tanaka
Osvaldo Chara
Spatiotemporal control of cell cycle acceleration during axolotl spinal cord regeneration
eLife
axolotl
spinal cord regeneration
computational model
cell proliferation
FUCCI
cell cycle
title Spatiotemporal control of cell cycle acceleration during axolotl spinal cord regeneration
title_full Spatiotemporal control of cell cycle acceleration during axolotl spinal cord regeneration
title_fullStr Spatiotemporal control of cell cycle acceleration during axolotl spinal cord regeneration
title_full_unstemmed Spatiotemporal control of cell cycle acceleration during axolotl spinal cord regeneration
title_short Spatiotemporal control of cell cycle acceleration during axolotl spinal cord regeneration
title_sort spatiotemporal control of cell cycle acceleration during axolotl spinal cord regeneration
topic axolotl
spinal cord regeneration
computational model
cell proliferation
FUCCI
cell cycle
url https://elifesciences.org/articles/55665
work_keys_str_mv AT emanuelcuracosta spatiotemporalcontrolofcellcycleaccelerationduringaxolotlspinalcordregeneration
AT leootsuki spatiotemporalcontrolofcellcycleaccelerationduringaxolotlspinalcordregeneration
AT aidarodrigoalbors spatiotemporalcontrolofcellcycleaccelerationduringaxolotlspinalcordregeneration
AT ellymtanaka spatiotemporalcontrolofcellcycleaccelerationduringaxolotlspinalcordregeneration
AT osvaldochara spatiotemporalcontrolofcellcycleaccelerationduringaxolotlspinalcordregeneration