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Pelzer, Diane; Phipps, Lauren S; Thuret, Raphael; Gallardo‐Dodd, Carlos J; Baker, Syed Murtuza; Dorey, Karel
EMBO reports, 06 September 2021, Letnik: 22, Številka: 9Journal Article
Xenopus tadpoles have the ability to regenerate their tails upon amputation. Although some of the molecular and cellular mechanisms that globally regulate tail regeneration have been characterised, tissue‐specific response to injury remains poorly understood. Using a combination of bulk and single‐cell RNA sequencing on isolated spinal cords before and after amputation, we identify a number of genes specifically expressed in the spinal cord during regeneration. We show that Foxm1, a transcription factor known to promote proliferation, is essential for spinal cord regeneration. Surprisingly, Foxm1 does not control the cell cycle length of neural progenitors but regulates their fate after division. In foxm1−/− tadpoles, we observe a reduction in the number of neurons in the regenerating spinal cord, suggesting that neuronal differentiation is necessary for the regenerative process. Altogether, our data uncover a spinal cord‐specific response to injury and reveal a new role for neuronal differentiation during regeneration. Synopsis Differentiation of neural progenitor cells (NPCs) is a hallmark of successful spinal cord regeneration. This study shows that Foxm1 controls the switch from proliferation to differentiation of NPCs during spinal cord regeneration in Xenopus tropicalis. A regeneration‐specific population of cells, characterized by the expression of foxm1, was identified during spinal cord regeneration using single cell RNA sequencing. Foxm1−/− tadpoles do not fully regenerate their spinal cord and tail after amputation. Foxm1 promotes neuronal differentiation during regeneration, without affecting proliferation or the overall length of the cell cycle in NPCs. Differentiation of neural progenitor cells (NPCs) is a hallmark of successful spinal cord regeneration. This study shows that Foxm1 controls the switch from proliferation to differentiation of NPCs during spinal cord regeneration in Xenopus tropicalis.
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