RT Journal Article SR Electronic T1 The West African lungfish provides insights into the evolution of tetrapod tail regeneration JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.02.12.946319 DO 10.1101/2020.02.12.946319 A1 Kellen Matos Verissimo A1 Louise Neiva Perez A1 Aline Cutrim Dragalzew A1 Gayani Senevirathne A1 Sylvain Darnet A1 Wainna Renata Barroso Mendes A1 Ciro Ariel dos Santos Neves A1 Erika Monteiro dos Santos A1 Cassia Nazare de Sousa Moraes A1 Neil Shubin A1 Nadia Belinda Frobisch A1 Josane de Freitas Sousa A1 Igor Schneider YR 2020 UL http://biorxiv.org/content/early/2020/02/13/2020.02.12.946319.abstract 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.