Abstract: 

Instead of obeying their fated polyp-to-medusa life cycle, some jellyfish species challenge the deep-rooted perspective of unidirectional growth-to-death development trajectory by undergoing remarkable medusa-to-polyp life cycle reversal when encountering fatal damages. Although this reverse development (RD) ability was frequently highlighted as the embodiment of biological immortality and generating numerous research interests, its underlying mechanism is largely opaque due to the lack of an integrated histological, omics, and functional verification framework. In this study, we introduced a novel Hong Kong indigenous hydrozoa species with robust RD ability, Cirrholovenia tainiula sp. nov., and aimed to utilize it as our model organism for RD research. We established a culture system, observed its life cycle, recorded several RD inducers and detailed RD process. By integrating a high-quality genome with time-series transcriptome dataset, comparative genomics and transcriptomic analysis hinted an independent RD evolutionary trajectory among hydrozoan phylogeny, several expansions in some key gene families (e.g. apoptosis, genetic fidelity, development), as well temporal functional regulatory modules governing RD. Via the first-in-Cnidaria tissue clearing application alongside classical developmental techniques (e.g. TUNEL, EdU, HCR-FISH), we obtained a spatiotemporal atlas of tissue rearrangement during RD. Further RNAi and drug administration experiments also yielded promising defective RD phenotypes by manipulating candidate genes and pathways (e.g. SOXB2, MAPK signaling network, as well as canonical Wnt/β-catenin signaling pathway). Overall, our pioneering study established C. tainiula sp. nov. as a promising model system for study of regeneration, rejuvenation, and biological immortality.