DSP1 regulates planarian (Dugesia japonica) neural regeneration depending on CnB

Regeneration and repair of the injured central nervous system is a major focus in biological research, yet many key questions remain unanswered, making it essential to explore the mechanisms underlying neural regeneration. Dorsal switch protein 1 (DSP1) plays critical roles in embryonic development and immune regulation in multiple invertebrates including Drosophila, whereas its vertebrate ortholog HMGB1 participates in diverse biological processes; however, its function in central nervous system regeneration has not been reported. In this study, we found that DSP1 was widely expressed in the intact planarian, predominantly in parenchyma, retropharyngeal and cephalic ganglia. Knockdown of DSP1 promoted blastema growth at one dpa, without affecting the stem cell population. Silencing of DSP1 accelerated brain regeneration and significantly increased the number of daughter cells derived from stem cells, accompanied by downregulated expression of calcineurin subunit B (CnB), a Wnt signaling pathway gene. Notably, simultaneous knockdown of DSP1 and CnB promoted blastema regeneration. These findings suggest DSP1 is associated with CnB to regulate neural regeneration in planarian. These findings provide a theoretical basis for understanding the DSP1/CnB signaling axis in regulating neural regeneration in mammals, and have important implications for the development of drugs targeting neuronal regeneration.