Unravelling Genomic Signatures of lncRNA Expression in Zebrafish Caudal Fin Regeneration: Bridging Regenerative Potential and Positional Memory

Using zebrafish as a model, we characterized novel long non-coding RNAs linked to caudal fin regeneration and positional memory, uncovering evolutionarily conserved candidates with potential cross-species relevance. RNA-seq data deposited in the NCBI database were compared at various important time points (0h post-amputation (hpa), 12 hpa, 1 day post-amputation (dpa), two dpa, three dpa, and seven dpa) and fin parts (proximal, middle, and distal) to uncover major regulatory lncRNAs. Using HISAT2, StringTie, FEELnc, Conservation Analysis, and WGCNA, our analysis revealed 107 lncRNAs associated with specific regeneration time points and 229 lncRNAs involved in positional memory during the regenerative process. We identified 13 common genomic regions that are complete or partial lncRNAs, indicating a functional connection between regeneration and positional identity, and expressed differently at each time point and each position. Additionally, a comparison with regeneration-associated mRNAs revealed that these 13 regions play critical roles in both processes, providing insights into the molecular mechanisms of regenerative precision. RT-PCR validation confirmed position-specific differential expression of these overlapping regions despite identical injury, suggesting roles in regenerative regulation and evolutionary adaptation.