title: Planar cell polarity-mediated induction of neural stem cell expansion during axolotl spinal cord regeneration.
abstract: Axolotls are uniquely able to mobilize neural stem cells to regenerate all missing regions of the spinal cord. How a neural stem cell under homeostasis converts after injury to a highly regenerative cell remains unknown. Here, we show that during regeneration, axolotl neural stem cells repress neurogenic genes and reactivate a transcriptional program similar to embryonic neuroepithelial cells. This dedifferentiation includes the acquisition of rapid cell cycles, the switch from neurogenic to proliferative divisions, and the re-expression of planar cell polarity (PCP) pathway components. We show that PCP induction is essential to reorient mitotic spindles along the anterior-posterior axis of elongation, and orthogonal to the cell apical-basal axis. Disruption of this property results in premature neurogenesis and halts regeneration. Our findings reveal a key role for PCP in coordinating the morphogenesis of spinal cord outgrowth with the switch from a homeostatic to a regenerative stem cell that restores missing tissue.
authors.affiliation: Deutsche Forschungsgemeinschaft - Center for Regenerative Therapies Dresden, Dresden, Germany.|Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.|Technische Universität Dresden, 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.|Technische Universität Dresden, Dresden, Germany.
authors.forename: Akira
authors.identifier: http://orcid.org/0000-0002-7151-0089
authors.initials: A
authors.lastname: Tazaki
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.|Technische Universität Dresden, Dresden, Germany.
authors.forename: Sergej
authors.initials: S
authors.lastname: Nowoshilow
authors.affiliation: Center for Information Services and High Performance Computing, Technische Universität Dresden, Dresden, Germany.|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.initials: O
authors.lastname: Chara
authors.affiliation: Deutsche Forschungsgemeinschaft - Center for Regenerative Therapies Dresden, Dresden, Germany.|Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.|Technische Universität Dresden, Dresden, Germany.
authors.forename: Elly M
authors.initials: EM
authors.lastname: Tanaka
mesh_terms: D000558:Ambystoma mexicanum; D000818:Animals; D016764:Cell Polarity; D049109:Cell Proliferation; D058953:Neural Stem Cells / Q000502:physiology*; D058630:Spinal Cord Regeneration
keywords: axolotl; cell biology; developmental biology; neural stem cells; planar cell polarity; regeneration; spinal cord; stem cells