COMPRENDO: Focus and approach

Tens of thousands of man-made chemicals are in regular use and discharged into the environment. Many of them are known to interfere with the hormonal systems in humans and wildlife. Given the complexity of endocrine systems, there are many ways in which endocrine-disrupting chemicals (EDCs) can affect the body’s signaling system, and this makes unraveling the mechanisms of action of these chemicals difficult. A major concern is that some of these EDCs appear to be biologically active at extremely low concentrations. There is growing evidence to indicate that the guiding principle of traditional toxicology that “the dose makes the poison” may not always be the case because some EDCs do not induce the classical dose–response relationships. The European Union project COMPRENDO (Comparative Research on Endocrine Disrupters—Phylogenetic Approach and Common Principles focussing on Androgenic/Antiandrogenic Compounds) therefore aims to develop an understanding of potential health problems posed by androgenic and antiandrogenic compounds (AACs) to wildlife and humans by focusing on the commonalities and differences in responses to AACs across the animal kingdom (from invertebrates to vertebrates)

Inhibition of cell proliferation does not slow down echinoderm neural regeneration

BACKGROUND: Regeneration of the damaged central nervous system is one of the most interesting post-embryonic developmental phenomena. Two distinct cellular events have been implicated in supplying regenerative neurogenesis with cellular material – generation of new cells through cell proliferation and recruitment of already existing cells through cell migration. The relative contribution and importance of these two mechanisms is often unknown. METHODS: Here, we use the regenerating radial nerve cord (RNC) of the echinoderm Holothuria glaberrima as a model of extensive post-traumatic neurogenesis in the deuterostome central nervous system. To uncouple the effects of cell proliferation from those of cell migration, we treated regenerating animals with aphidicolin, a specific inhibitor of S-phase DNA replication. To monitor the effect of aphidicolin on DNA synthesis, we used BrdU immunocytochemistry. The specific radial glial marker ERG1 was used to label the regenerating RNC. Cell migration was tracked with vital staining with the lipophilic dye DiI. RESULTS: Aphidicolin treatment resulted in a significant 2.1-fold decrease in cell proliferation. In spite of this, the regenerating RNC in the treated animals did not differ in histological architecture, size and cell number from its counterpart in the control vehicle-treated animals. DiI labeling showed extensive cell migration in the RNC. Some cells migrated from as far as 2 mm away from the injury plane to contribute to the neural outgrowth. CONCLUSIONS: We suggest that inhibition of cell division in the regenerating RNC of H. glaberrima is compensated for by recruitment of cells, which migrate into the RNC outgrowth from deeper regions of the neuroepithelium. Neural regeneration in echinoderms is thus a highly regulative developmental phenomenon, in which the size of the cell pool can be controlled either by cell proliferation or cell migration, and the latter can neutralize perturbations in the former. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12983-017-0196-y) contains supplementary material, which is available to authorized users

Regeneration in Echinoderms: repair, regrowth, cloning

Regenerative potential is expressed to a maximum extent in echinoderms. It is a commonphenomenon in all the classes, extensively employed to reconstruct external appendages and internalorgans often subjected to amputation, self-induced or traumatic, rapidly followed by completesuccessful re-growth of the lost parts. Regeneration has been studied in adult individuals as well as inlarvae. In armed echinoderms, regeneration of arms is obviously frequent: in many cases, thedetached body fragments can undergo phenomena of partial or total regeneration independently of thedonor animal, and, in a few cases (asteroids), the individual autotomised arms can even regenerate toproduce new complete adults, offering superb examples of cloning strategies. In the species examinedso far most results throw light on aspects related to wound healing, growth, morphogenesis anddifferentiation, even though in most cases many crucial questions remain unanswered. The presentpaper provides an overview of the current understanding of the phenomenon and covers the mainbiological aspects of regeneration giving an idea of the “state of the art” across the phylum in terms ofexperimental approaches and representative models

Expression of Tgf-beta in the regenerative process of crinoid echinoderms

For many years, we focused our studies on the remarkable power of regeneration exhibited by crinoid echinoderms. Current investigations are exploring the aspects related to the 'putative' growth factors crucial for the regenerative process in crinoids. Due to its importance in wound healing phenomena of vertebrates and invertebrates, both in the embryo and in adults, the present study concentrates on the possible presence/expression and roles of TGF-\u3b2 in arm regeneration processe of the crinoid Antedon mediterranea. This problem has been explored by employing 1) a biochemical and immunocytochemical approach, which allowed us to detect the presence of TGF-\u3b21 and its putative changes of pattern distribution during the regeneration process; 2) a molecular approach, thanks to which we cloned a BMP2/4 homologue from crinoids (AnBMP2/4) confirming the possible presence of different genes of the TGF-\u3b2 superfamily. Expression studies indicate an important role for AnBMP2/4 during the more advanced stages of regeneration at a time when new tissues are being established and the brachial nerve is extending into the regenerate. This expression in an \u2018adult\u2019 regenerating system shows remarkable parallels with recent investigations in sea urchin embryos where a BMP2/4 homologue is involved in the regulation of the ectoderm/endoderm boundary and epidermal/non epidermal fate decisions. Our results suggest in particular that AnBMP2/4 plays an important role in crinoid skeletogenesis as well as in neurogenesis and support the idea of an evolutionary developmental programme where essential gene families are conserved throughout phylogeny both in terms of expression and function. The future employment of techniques such as RNA interference or bead implantation, in adult echinoderms, will be of fundamental importance to understand the function of AnBMP2/4 and other related genes

Growth factors, heat shock proteins and regeneration in echinoderms

The study of regeneration in armed echinoderm species, including crinoids, ophiuroids and asteroids, is attracting increasing attention. Recent interest has focused on the presence and potential role of growth factors, including members of the nerve growth factor (NGF) and transforming growth factor-beta (TGF-beta) families, in the regenerative process and their possible relationship to the normal developmental (ontogenetic) regulatory cascade. In addition, the expression patterns of the heat-shock family of stress proteins (Hsps) during regeneration are also important. Their role forms part of a normal stress response to the trauma of autotomy in combination with a putative function in tissue remodelling and associated protein turnover during regeneration. The temporal dynamics of the stress response may also be strongly indicative of environmentally adaptive pressures operating on these systems