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Abstract
Which genes and gene signaling pathways mediate regenerative processes? In recent years, multiple studies, using a variety of animal models, have aimed to answer this question. Some answers have been obtained from transcriptomic and genomic studies where possible gene and gene pathway candidates thought to be involved in tissue and organ regeneration have been identified. Several of these studies have been done in echinoderms, an animal group that forms part of the deuterostomes along with vertebrates. Echinoderms, with their outstanding regenerative abilities, can provide important insights into the molecular basis of regeneration. Here we review the available data to determine the genes and signaling pathways that have been proposed to be involved in regenerative processes. Our analyses provide a curated list of genes and gene signaling pathways and match them with the different cellular processes of the regenerative response. In this way, the molecular basis of echinoderm regenerative potential is revealed, and is available for comparisons with other animal taxa.
FIGURE 1. Representative of the five classes in the Echinodermata phylum that have been used in regeneration studies. (A) Crinoidea represented by the feather star Antedon mediterranea. (B) Echinoidea represented by the sea urchin Lytechinus variegatus. (C) Asteroidea represented by the sea star Asterias rubens. (D) Ophiuroidea represented by the brittle star Amphiura filiformis. (E) Holothuroidea represented by the sea cucumber Holothuria glaberrima.
FIGURE 2. Molecular studies of regeneration favor certain echinoderm classes over others. Extensive studies have been done in ophiuroids and holothuroids. Asteroids and crinoids have been less studied at the molecular level, even though their regeneration prowess is well known, and histological and cellular analyses of their arm regeneration are available. Molecular studies in echinoids are also limited, mainly because their regenerative capabilities are the least impressive when compared to those from other classes.
FIGURE 3. Pharmacological studies in brittle star arm regeneration and sea cucumber intestinal regeneration. (A) Stages of arm regeneration in the brittle star A. filiformis provide a baseline to detect the effect of regeneration modulating drugs as shown in Czarkwiani et al. (2016). (B) The effect of a FGF inhibitor in a study by Czarkwiani et al. (2021) is shown by a decrease in the extension of the regenerating arm and by the inhibition of formation of the spicules that form the skeleton. (C) Stages of intestinal regeneration in the sea cucumber H. glaberrima provide a baseline to detect the effect of regeneration modulating drugs as shown in García-Arrarás et al., 2019. (D) Results from Bello et al. (2020) on the effect of Wnt inhibitors (iCRT14) and activators (LiCl) is determined in the size of the regenerating gut rudiment when compared to those of vehicle treated controls.
