Salamander-like tail regeneration in the West African lungfish

Abstract

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.

Sequencing and chromosome-scale assembly of the giantPleurodeles waltlgenome

“…These include ZBED6, a transcription factor involved in muscle development (Markljung et al, 2009), ZBED1, a putative transcriptional regulator of cell proliferation and ribosomal gene expression (Yamashita et al, 2007), and ZBED4, a retina-associated factor (Saghizadeh et al, 2009), isoforms of which are found significantly upregulated during blastema formation. The latter is of particular interest in light of a previous report of ZBED4 upregulation in lungfish tail blastemas (Verissimo et al, 2020). A number of ZBED isoforms are also differentially expressed across additional P. waltl tissues, including in the germline (Suppl.…”

Biodiversity-based development and evolution: the emerging research systems in model and non-model organisms

“…The first group is the key species of a phylogeny with adaptations, or an evolutionary intermediate species. For example, the lungfish, representing a type of essential transition from aquatic to terrestrial vertebrates, can complete fin and tail regeneration (Conant, 1973;Verissimo et al, 2020), but whether it has a similar cardiac regenerative capacity following injury is unknown. Recently, an elegant study using systematic comparison of African killifish and zebrafish, demonstrated that evolutionary conserved regeneration-responsive enhancer elements exist, and tightly modulate regenerative capacities in vertebrates (Wang et al, 2020a).…”