Deep evolutionary origin of limb and fin regeneration

Abstract

Salamanders and lungfishes are the only sarcopterygians (lobe-finned vertebrates) capable of complete limb and paired fin regeneration, respectively. Among actinopterygians (ray-finned fishes), regeneration after amputation at the fin endoskeleton has only been demonstrated in Polypterid fishes (Cladistia). Whether complete appendage regeneration in sarcopterygians and actinopterygians evolved independently or has a common origin remains unknown. Here we combine fin regeneration assays and comparative RNA-seq analysis to provide support for a common origin of a paired appendage regeneration in osteichthyes (bony vertebrates).We show that, in addition to Polypterids, regeneration after fin endoskeleton amputation occurs in extant representatives of all major actinopterygian clades: the American paddlefish, (Chondrostei), the spotted gar (Holostei), as well as in two cichlid species, the white convict and the oscar (Teleostei). 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 pan-osteichthyes genetic program of appendage regeneration.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. Δ ΔCT method. methods 25, 402-408 (2001).

Appendage regeneration in anamniotes utilizes genes active during larval‐metamorphic stages that have been lost or altered in amniotes: The case for studying lizard tail regeneration

“…Fish and amphibians can variably regenerate numerous organs and this capability is also present in ancestral but extant fish (Cuervo, Hernandez-Martinez, Chimal-Monroy, Merchant-Larios, & Covarrubias, 2012;Darnet et al, 2019;Lu et al, 2019;Mescher, 1996;Niazi, 1963;Nikiforova & Golichennkov, 2012;Wagner & Misof, 1992). It is here hypothesize that regeneration was likely largely distributed among early fish of the Silurian and Devonian such as ostracoderms, placoderms, acanthodes, paleonischoids, as suggested by recent morphological, molecular and paleontological discoveries (Cuervo et al, 2012;Nikiforova & Golichennkov, 2012;Darnet et al, 2019;Lu et al, 2019;Figure 2a,b). In the late Devonian, a group of fish, the sarcopterygians, evolved limbs and gave rise to the first terrestrial vertebrates, the labyrinthodont amphibians which flourished in the Carboniferous.…”

“…In the late Devonian, a group of fish, the sarcopterygians, evolved limbs and gave rise to the first terrestrial vertebrates, the labyrinthodont amphibians which flourished in the Carboniferous. It is likely that also these peculiar fish were capable of broad organ regeneration, including in the fins, as this process is still present in larval and adults of extant dipnoi (Conant, 1970(Conant, , 1972Darnet et al, 2019;Nogueira et al, 2016). Some information, including those derived from the fossil record, indicate that also ancient amphibians went through larval stages during their life cycles, stages needed to transit toward a terrestrial life (Darnet et al, 2019;Fröbisch, Bickelmann, Olori, & Witzmann, 2015;Frobisch, Bickelmann, & Witzmann, 2014;van der Vos, Witzmann, & Frobish, 2017).…”

“…It is likely that also these peculiar fish were capable of broad organ regeneration, including in the fins, as this process is still present in larval and adults of extant dipnoi (Conant, 1970(Conant, , 1972Darnet et al, 2019;Nogueira et al, 2016). Some information, including those derived from the fossil record, indicate that also ancient amphibians went through larval stages during their life cycles, stages needed to transit toward a terrestrial life (Darnet et al, 2019;Fröbisch, Bickelmann, Olori, & Witzmann, 2015;Frobisch, Bickelmann, & Witzmann, 2014;van der Vos, Witzmann, & Frobish, 2017). Aquatic amphibians (urodeles) retained the large genomes present in their ancestor sarcopterigians (Figure 2c), also present in extant lungfishes (Conant, 1970(Conant, , 1972Nogueira et al, 2016, Darnet et al, 2019.…”

“…Some information, including those derived from the fossil record, indicate that also ancient amphibians went through larval stages during their life cycles, stages needed to transit toward a terrestrial life (Darnet et al, 2019;Fröbisch, Bickelmann, Olori, & Witzmann, 2015;Frobisch, Bickelmann, & Witzmann, 2014;van der Vos, Witzmann, & Frobish, 2017). Aquatic amphibians (urodeles) retained the large genomes present in their ancestor sarcopterigians (Figure 2c), also present in extant lungfishes (Conant, 1970(Conant, , 1972Nogueira et al, 2016, Darnet et al, 2019. Therefore, among the peculiar adaptations of amphibians that are part of their biology, there was also a highly capability to recover from injuries, as documented by the fossil record.…”

“…Comparative transcriptome studies have shown that common genes and pathways are activated during fin, limb and tail regeneration in different groups of fish (Darnet et al, 2019;Katogi et al, 2004;Lu et al, 2019;Nogueira et al, 2016;Yoshinari et al, 2009), amphibians (Grow et al, 2006;Monagan et al, 2012;Stewart et al, 2013;Wu, Tsai, Ho, Chen, & Lee, 2013;Kochegarov et al, 2015;Tsujioka et al, 2015;Bryant et al, 2017;Elewa et al, 2017), and lizards (Hutchins et al, 2014;Hutchins, Eckalbar, et al, 2016;Hutchins, Wilson-Rawls, & Kusumi, 2016;Vitulo et al, 2017aVitulo et al, , 2017b. Table 3 only (Figure 5b; Table 5).…”