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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.

SUBMITTER: Rodrigo Albors A 

PROVIDER: S-EPMC4755742 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Planar cell polarity-mediated induction of neural stem cell expansion during axolotl spinal cord regeneration.

Rodrigo Albors Aida A   Tazaki Akira A   Rost Fabian F   Nowoshilow Sergej S   Chara Osvaldo O   Tanaka Elly M EM  

eLife 20151114


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 pro  ...[more]

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