Deciphering the ancestral mechanisms of neural regeneration through single-cell analyses of jellyfish rhopalium repair

The rhopalium, an early specialized centralized nervous structure in medusozoans, exhibits a remarkable regenerative capacity after removal, offering a unique model for investigating the ancestral regulatory logic of neural regeneration. However, the cellular and molecular mechanisms underlying the process remain unknown. Here, we defined distinct stages of rhopalium regeneration in the jellyfish <i>Aurelia coerulea</i> and constructed a stage-specific cell landscape and gene regulatory networks. Notably, we identified a population of wound-induced cells that emerges rapidly postinjury and activates Wnt signaling to initiate blastema formation; cross-species comparisons revealed that this regulatory mechanism is conserved across metazoans. We further identified that retinoic acid signaling is essential for photoreceptor regeneration and ocelli reconstruction. The findings presented herein uncover the ancestral regulatory mechanisms governing neural regeneration in the early centralized nervous system, providing insights into the common evolutionary origins of neural repair across organisms.