From injury to recovery: Transcriptomic dynamics in Zebrafish brain regeneration

Regeneration of damaged brain tissue is a complex biological process that varies significantly across species. Zebrafish possess a remarkable ability to regenerate central nervous system structures, making them an invaluable model for studying the molecular and cellular mechanisms underlying neuroregeneration. In this study, we employed a previously standardized telencephalic stab wound injury model to investigate transcriptional and cellular responses during zebrafish brain regeneration. This well-characterized model allows for precise analysis of injury-induced regenerative processes by comparing different temporal stages of recovery. Using RNA sequencing at four key time points: control, 1 day post-lesion, 4 dpl, and 7 dpl, we identified dynamic changes in gene expression and revealed critical signaling pathways associated with regeneration. Among these, the p38 MAPK signaling cascade emerged as a key regulator. Our findings underscore the multifaceted role of p38 MAPK, which modulates progenitor cell proliferation, differentiation, and neurogenesis during regeneration. These insights align with known roles of p38 MAPK in neural stem cell biology while highlighting its distinct contributions in a regenerative context. This work provides a comprehensive overview of early transcriptional events and highlights novel molecular players involved in CNS repair, further establishing the zebrafish as a robust model for regenerative research. Our findings open avenues for applying these pathways to develop therapeutic strategies aimed at enhancing brain repair in humans.