Stat3 has a different role in axon growth during development than it does in axon regeneration after injury

Abstract As a pleiotropic factor, signal transducer and activator of transcription 3 (STAT3) has been implicated in both neural development and regeneration. Here, we demonstrate that Stat3 plays distinct roles in PLL axon embryonic growth and regeneration using zebrafish posterior lateral line (PLL) axons. Mutation of stat3 rather than Jak/Stat inhibition resulted in PLL axons truncation during embryonic growth. We found that Stat3 was co-localized with mitochondria in PLL axon and the ATPase activity and mitochondrial membrane potential was decreased in stat3 mutant and mitochondria agonist partially rescued PLL axon growth in stat3 mutant indicating Stat3 regulated PLL axon growth through mitochondrial Stat3 function. By contrast, Jak/Stat signaling inhibitors retarded PLL axon regeneration and Schwann cell migration. Stat3 promotes PLL axon regeneration mainly through regulating Schwann cell migration via Jak/Stat signaling. We provide a new mechanism of Stat3 in axon growth and regeneration and suggest that Stat3 is a promising therapeutic target for neural regeneration.