Full regeneration of the tribasal Polypterus fin

Abstract

Full limb regeneration is a property that seems to be restricted to urodele amphibians. Here we found that Polypterus , the most basal living ray-finned fish, regenerates its pectoral lobed fins with a remarkable accuracy. Pectoral Polypterus fins are complex, formed by a well-organized endoskeleton to which the exoskeleton rays are connected. Regeneration initiates with the formation of a blastema similar to that observed in regenerating amphibian limbs. Retinoic acid induces dose-dependent phenotypes ranging from inhibition of regeneration to apparent anterior–posterior duplications. As in all developing tetrapod limbs and regenerating amphibian blastema, Sonic hedgehog is expressed in the posterior mesenchyme during fin regeneration. Hedgehog signaling plays a role in the regeneration and patterning processes: an increase or reduction of fin bony elements results when this signaling is activated or disrupted, respectively. The tail fin also regenerates but, in contrast with pectoral fins, regeneration can resume after release from the arrest caused by hedgehog inhibition. A comparative analysis of fin phenotypes obtained after retinoic acid treatment or altering the hedgehog signaling levels during regeneration allowed us to assign a limb tetrapod equivalent segment to Polypterus fin skeletal structures, thus providing clues to the origin of the autopod. We propose that appendage regeneration was a common property of vertebrates during the fin to limb transition.

Tetrapod limb and sarcopterygian fin regeneration share a core genetic programme

“…Complete fin regeneration observed in Polypterus suggests that appendage regeneration may have evolved at the base of all bony fish10, nevertheless, little is known of the molecular mechanisms underlying Polypterus fin regeneration. Limited appendage regeneration capacities are also observed in teleost fish and mammals, which can regenerate fin rays and digit tips, respectively, but not the endochondral elements31.…”

“…For further lungfish transcriptome characterization, transcripts were clustered by human orthologs using BLASTx against Human NCBI Refseq database (11/2014), with an e-value of 10 −10 , as described for a previous axolotl transcriptome10. For each human homologue gene cluster (HHGC), expression was calculated in TPM for the six conditions based on the read count sum of lungfish transcripts included in the cluster.…”

“…Nevertheless, it remains unclear whether urodele LSGs are causally linked to the origin of limb regeneration or were integrated into a pre-existing regenerative programme. Appendage regeneration is also observed in living sarcopterygian (lobe-finned) fish such as the African lungfish Protopterus 9 and could have an even deeper origin, since basal actinopterygian (ray-finned) fish of the genus Polypterus can fully regenerate paired appendages, including the endochondral skeleton10 (Fig. 1a).…”

Molecular Insight into the Association Between Cartilage Regeneration and Ear Wound Healing in Genetic Mouse Models: Targeting New Genes in Regeneration

“…Regeneration potential is phylogenetically dispersed among animal taxa and is a basal trait in vertebrates, including fishes, amphibians, and mammalian fetal tissues (Gierer et al 1972; Stocum 1984; Fini 1999; Harty et al 2003; Tanaka 2003; Bely 2010; Cuervo et al 2012; Seifert et al 2012). A consensus is that the regenerative capability in adult mammals is extremely limited (ten Koppel et al 2001; Harty et al 2003; Carlson 2005; Colwell et al 2005; Sanchez Alvarado and Tsonis 2006; Kierdorf and Kierdorf 2011).…”

A Regeneration Toolkit

“…Bichirs ( Polypterus ) are an air-breathing species considered the most basal of remaining actinopterygian fish, sharing some features with extinct and extant tetrapod species. Bichirs regenerate after amputation injuries to their lobed pectoral fins and also display regenerative responses to cardiac injury (Cuervo et al, 2012; Kikuchi et al, 2011; King and Yin, 2016). Though not maintained as lab colonies, bichirs could be an informative model for questions that address the evolution of regenerative capacity.…”