Deep evolutionary origin of limb and fin regeneration

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 116; no. 30; pp. 15106 - 15115
• Main Authors: Darnet, Sylvain, Dragalzew, Aline C., Amaral, Danielson B., Sousa, Josane F., Thompson, Andrew W., Cass, Amanda N., Lorena, Jamily, Pires, Eder S., Costa, Carinne M., Sousa, Marcos P., Fröbisch, Nadia B., Oliveira, Guilherme, Schneider, Patricia N., Davis, Marcus C., Braasch, Ingo, Schneider, Igor
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 23-07-2019
• Series: PNAS Plus
• Subjects: Actinopterygii; Ambystoma mexicanum - classification; Ambystoma mexicanum - genetics; Amputation; Animal Fins - physiology; Animals; Biological Evolution; Biological Sciences; Cichlids - classification; Cichlids - genetics; Cladistia; Cyprinidae - classification; Cyprinidae - genetics; Endoskeleton; Evolution; Extremities - physiology; Fish Proteins - classification; Fish Proteins - genetics; Fishes - classification; Fishes - genetics; Gene Ontology; Gene sequencing; Limb buds; Molecular Sequence Annotation; Osteichthyes; Phylogeny; PNAS Plus; Polypterus; Regeneration (physiology); Regeneration - genetics; Ribonucleic acid; RNA; Sarcopterygii; Transcriptome; Vertebrates; limb; fin; evolution; regeneration; tetrapod
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1900475116

Salamanders and lungfishes are the only sarcopterygians (lobe-finned vertebrates) capable of paired appendage regeneration, regardless of the amputation level. Among actinopterygians (ray-finned fishes), regeneration after amputation at the fin endoskeleton has only been demonstrated in polypterid fishes (Cladistia). Whether this ability evolved independently in sarcopterygians and actinopterygians or has a common origin remains unknown. Here we combine fin regeneration assays and comparative RNA-sequencing (RNA-seq) analysis of Polypterus and axolotl blastemas to provide support for a common origin of paired appendage regeneration in Osteichthyes (bony vertebrates). We show that, in addition to polypterids, regeneration after fin endoskeleton amputation occurs in extant representatives of 2 other nonteleost actinopterygians: the American paddlefish (Chondrostei) and the spotted gar (Holostei). Furthermore, we assessed regeneration in 4 teleost species and show that, with the exception of the blue gourami (Anabantidae), 3 species were capable of regenerating fins after endoskeleton amputation: the white convict and the oscar (Cichlidae), and the goldfish (Cyprinidae). Our comparative RNA-seq analysis of regenerating blastemas of axolotl and Polypterus reveals the activation of common genetic pathways and expression profiles, consistent with a shared genetic program of appendage regeneration. Comparison of RNA-seq data from early Polypterus blastema to single-cell RNA-seq data from axolotl limb bud and limb regeneration stages shows that Polypterus and axolotl share a regeneration-specific genetic program. Collectively, our findings support a deep evolutionary origin of paired appendage regeneration in Osteichthyes and provide an evolutionary framework for studies on the genetic basis of appendage regeneration.