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 Hoodia 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 Blushes 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.