JAK‐STAT pathway activation in response to spinal cord injury in regenerative and non‐regenerative stages of Xenopus laevis

Xenopus laevis tadpoles can regenerate the spinal cord after injury but this capability is lost during metamorphosis. Comparative studies between pre-metamorphic and metamorphic Xenopus stages can aid towards understanding the molecular mechanisms of spinal cord regeneration. Analysis of a previous transcriptome-wide study suggests that, in response to injury, the JAK-STAT pathway is differentially activated in regenerative and non-regenerative stages. We characterized the activation of the JAK-STAT pathway and found that regenerative tadpoles have an early and transient activation. In contrast, the non-regenerative stages have a delayed and sustained activation of the pathway. We found that STAT3 is activated in response to injury mainly in Sox2/3+ ependymal cells, motoneurons and sensory neurons. Finally, to study the role of temporal activation we generated a transgenic line to express a constitutively active version of STAT3. The sustained activation of the JAK-STAT pathway in regenerative tadpoles reduced the expression of pro-neurogenic genes normally upregulated in response to spinal cord injury, suggesting that activation of the JAK-STAT pathway modulates the fate of neural progenitors.