PT - JOURNAL ARTICLE AU - Kellen Matos Verissimo AU - Louise Neiva Perez AU - Aline Cutrim Dragalzew AU - Gayani Senevirathne AU - Sylvain Darnet AU - Wainna Renata Barroso Mendes AU - Ciro Ariel dos Santos Neves AU - Erika Monteiro dos Santos AU - Cassia Nazare de Sousa Moraes AU - Neil Shubin AU - Nadia Belinda Frobisch AU - Josane de Freitas Sousa AU - Igor Schneider TI - The West African lungfish provides insights into the evolution of tetrapod tail regeneration AID - 10.1101/2020.02.12.946319 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.02.12.946319 4099 - http://biorxiv.org/content/early/2020/02/13/2020.02.12.946319.short 4100 - http://biorxiv.org/content/early/2020/02/13/2020.02.12.946319.full AB - Salamanders, frog tadpoles, and lizards possess the remarkable ability to regenerate tails. The fossil record suggests that this capacity is an ancestral tetrapod trait, yet its evolutionary history remains unclear. Here we examine tail regeneration in a living representative of the sister group of tetrapods, the West African lungfish Protopterus annectens. We show that, as seen in salamanders, lungfish tail regeneration occurs via formation of a proliferative blastema and restores original structures including muscle, skeleton and spinal cord. Contrary to lizards and similar to salamanders, lungfish regenerate spinal cord neurons and reconstitute dorsoventral patterning of the tail. Similar to salamander and frog tadpoles, we show that Shh is required for lungfish tail regeneration. Through RNA-seq analysis of uninjured and regenerating tail blastema we show that lungfish deploy a genetic program comparable to that of tetrapods, showing upregulation of genes and signaling pathways previously implicated in amphibian and lizard tail regeneration. Furthermore, the tail blastema showed marked upregulation of genes encoding post-transcriptional RNA processing components and transposon-derived genes. Collectively, our study establishes the lungfish as a valuable research system for regenerative biology and provides insights into the evolution of cellular and molecular processes underlying vertebrate tail regeneration.