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

被引:56
作者
Albors, Aida Rodrigo [1 ,2 ,3 ]
Tazaki, Akira [1 ,2 ,3 ]
Rost, Fabian [4 ]
Nowoshilow, Sergej [1 ,2 ,3 ]
Chara, Osvaldo [4 ,5 ]
Tanaka, Elly M. [1 ,2 ,3 ]
机构
[1] Deutsch Forsch Gemeinschaft, Ctr Regenerat Therapies Dresden, Dresden, Germany
[2] Max Planck Inst Mol Cell Biol & Genet, Dresden, Germany
[3] Tech Univ Dresden, D-01062 Dresden, Germany
[4] Tech Univ Dresden, Ctr Informat Serv & High Performance Comp, D-01062 Dresden, Germany
[5] Univ Nacl La Plata, Natl Sci & Tech Res Council, Inst Phys Liquids & Biol Syst, RA-1900 La Plata, Buenos Aires, Argentina
关键词
MITOTIC SPINDLE ORIENTATION; CONVERGENT EXTENSION; DIVISION ORIENTATION; GLIAL-CELLS; GENE; GROWTH; EXPRESSION; TAIL; WNT; PROLIFERATION;
D O I
10.7554/eLife.10230
中图分类号
Q [生物科学];
学科分类号
090105 [作物生产系统与生态工程];
摘要
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.
引用
收藏
页数:29
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