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
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
Center for Information Services and High Performance Computing, Technische Universität Dresden, Dresden, Germany
Sergej Nowoshilow
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
Osvaldo Chara
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
Elly M Tanaka
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
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.
