Telomerase is essential for zebrafish heart regeneration. Hypoxia induces myocardial regeneration in zebrafish circulation. Regeneration is a complex biological process by which animals restore the shape, structure and function of body parts lost to injury or experiment brockes and kumar, 2005. Mammals have an extremely limited capacity to repair lost or damaged heart tissue, thus encouraging biologists to seek out models for heart regeneration. Here, we demonstrate histologically that zebrafish fully regenerate hearts within 2 months of 20% ventricular resection. We recently discovered myomixer, a musclespecific micropeptide required for myoblast fusion in mice. Zebrafish, which any of you who are fish fans here, keep. Its got a little heart with just two chambers, one atrium and one ventricle, and that pumps blood throughout the whole body, past the gills, which are the equivalent of a lung. Cell migration during heart regeneration in zebrafish ncbi nih. Electron microscopy shows a high degree of tissue remodeling of. Zebrafish heart regeneration as a model for cardiac tissue. Specific macrophage populations promote both cardiac scar. Our data provides the first direct evidence for the source of proliferating cardiomyocytes during zebrafish heart regeneration and indicates that stemprogenitor cells are not significantly involved in this.
In contrast to humans and other mammals, zebrafish hearts regenerate after substantial injury or tissue damage. Regeneration of the central nervous systemprinciples from brain regeneration in adult zebrafish. Regeneration of organs and appendages in zebrafish. Genetic ablation of regulatory tcells, which circulate and home to the injury site, impairs heart regeneration and other examples of tissue regeneration in zebrafish 27. In adult zebrafish and neonatal mice, heart regeneration occurs primarily through proliferation of preexisting cardiomyocytes 1, 2.
Dual roles of hydrogen peroxide in promoting zebrafish. For each image, single channel panels and the merge of the boxed region is provided. Evidence for hormonal control of heart regenerative. A dynamic epicardial injury response supports progenitor cell activity during zebrafish heart regeneration. Natural models of heart regeneration in lower vertebrates such as zebrafish are based on invasive surgeries causing mechanical injuries that are limited in size. Unlike humans, many lower vertebrates readily regenerate limbs, appendages and internal organs after injury. Tbx5a lineage tracing shows cardiomyocyte plasticity. Pdf 20 academic content and language evaluation of this article. Mammals respond to a myocardial infarction by irreversible scar formation. The exact source of these new cardiomyocytes is an unanswered question. Zebrafish, regeneration, scarring, heart failure, inflammation. Regenerated heart muscles come from proliferation of differentiated cardiomyocytes. Zebrafish, which any of you who are fish fans here, keep in the fish tank, can get to be about two inches long.
The zebrafish is an established model organism to study heart regeneration, in which preexisting cardiomyocytes proliferate to replace the lost. A combination of forward genetic screens, large clutch size, and external development has made the zebrafish a popular model system for ontogenetic development. Specifically, we show that pololike kinase1 plk1 is an essential component of cardiomyocyte proliferation during heart regeneration. Zebrafish models of cardiovascular disease springerlink. Recent work has shown that mg give rise to regenerated retinal neurons, but the role of resident microglia, and the innate immune system more generally, during retinal. Chla researchers discover a mechanism of heart regeneration in zebrafish. Requirement of the fusogenic micropeptide myomixer for. The formation of skeletal muscle fibers during embryogenesis and adult injuryinduced muscle repair occurs through the fusion of myoblasts. Zebrafish heart regeneration process uab barcelona. Cardiovascular disease cvd is one of the leading causes of death worldwide. Collectively, our study identifies h3k27me3mediated silencing of structural genes as requisite for zebrafish heart regeneration and suggests that repression of similar structural components in the border zone of an infarcted human heart might improve its regenerative capacity. Myomixer and myomaker, another musclespecific membrane protein, are sufficient to induce fusion of nonmuscle cells. Primary contribution to zebrafish heart regeneration by.
One of the most remarkable examples is heart regeneration ausoni and sartore, 2009. In contrast to mammals, zebrafish have the capacity to regenerate retinal neurons following a variety of injuries. An important mechanistic feature of zebrafish heart regeneration was revealed by recent. Most mammalian cardiomyocytes undergo polyploidization and permanently withdraw from the cellcycle postnatally, whereas lower vertebrates, such as newts and zebrafish, generally maintain 95% diploid mononucleated cardiomyocytes even as. During heart regeneration in zebrafish, lost ventricular tissues is rapidly replaced. The animation illustrates the steps in this regeneration process, highlighting the role of cell signaling proteins called fibroblast growth factors fgf. A metabolic switch from oxphos to glycolysis is essential. Here, we created a genetic cell ablation model in zebrafish that facilitates inducible destruction of a high percentage of cardiomyocytes. Advances in understanding the mechanism of zebrafish heart regeneration.
In particular, hypoxia is associated with cardiac ischemia. This is a pdf file of an unedited manuscript that has been. Zebrafish has been used extensively to study heart regeneration, resulting in the identification of proliferating cardiomyocytes that drive this. Zebrafish heart regeneration occurs by cardiomyocyte. Therefore, elucidating mechanisms of zebrafish heart regeneration. Cardiac injury in mammals and amphibians typically leads to scarring, with minimal regeneration of heart muscle. However, a damaged zebrafish heart can recover most of its original shape, size, and function over time. Complete tissue regeneration of multiple organs, including the heart, has been demonstrated in several vertebrate model systems such as the zebrafish. Zebrafish are able to efficiently regenerate lost cardiac muscle, and is used as a model to understand why natural heart regeneration is blocked in mammals. Herein, we investigate the effect of h 2 o 2 in recovery of aki using zebrafish model inducing by gentamicin. Notch signalling is required for zebrafish cardiac regeneration. A chemical biology approach to myocardial regeneration. It is not known how opposing cellular responses of fibrosis and new myocardium formation are spatially and temporally coordinated during heart regeneration in zebrafish. Stem cell research heart regeneration and rejuvenation.
The robust capacity of zebrafish to regenerate a variety of tissues position it as an ideal genetic model system for understanding the molecular and cellular events governing regeneration. In particular, our understanding of heart development has benefited greatly from zebrafish mutants that specifically disrupt cardiovascular form and function2931. The similar role of h 2 o 2 in promoting regeneration is also seen in zebrafish heart and fin 18,19. The zebrafish is an established model organism to study heart regeneration, in which preexisting cardiomyocytes proliferate to replace the lost myocardium 1,2,3. Autophagy activation in zebrafish heart regeneration. Renowned cardiologist helen taussig expressed concern in 1969 that it was not yet time for human trials, warning, our hope should be that physicians and surgeons will proceed with extreme caution until such time as a cardiac transplant will not announce the imminence of death but offer the patient the probability of a return to a useful life for a number of years. Zebrafish cardiomyocytes were assumed to be diploid based on their. The adult mammalian heart is minimally regenerative after injury, whereas neonatal hearts fully recover even after major damage. Neonatal mouse heart regeneration is similar to zebrafish heart regeneration, involving cardiomyocyte dedifferentiation and proliferation.
Pdf in vivo cardiac reprogramming contributes to zebrafish. While heart regeneration is generally very low in mammals, it can regenerate efficiently in certain amphibian and fish species 4,5. The regenerative capacity of the zebrafish heart is. By contrast, zebrafish are able to resolve the scar and to regenerate functional cardiac muscle. An important difference is that injuryinduced cardiogenesis occurs throughout the injured, growing organ in mice, whereas in hearts of mature zebrafish this response is focused at the injury site. By contrast, teleost fish and urodele amphibians are capable of heart regeneration after a partial amputation. Zebrafish heart regeneration developmental biology. The growing interest in zebrafish research was paralleled by an increase in tools and methods. Pdf despite current treatment regimens, heart failure remains the leading. Cellspecific depletion of over 60% of the ventricular myocardium triggered signs of cardiac. The capacity to regenerate damaged tissues, such as the heart, various enormously amongst species. The underlying problem, in essence, is that up to a billion cardiomyocytes can be lost after myocardial infarction and that endogenous regeneration cannot restore the heart s function, resulting in increased risk for death by heart disease. The zebrafish heart regenerates after cryoinjuryinduced. Migration of cardiomyocytes is essential for heart.
Teleosts, as urodele amphibians, have the remarkable capacity to regenerate several organs and structures of their body after an injury. Cardiac stem cell therapy and the promise of heart. Regeneration occurs through robust proliferation of cardiomyocytes localized at the leading epicardial edge of the new myocardium. Individual channels were merged in imagej software schneider et al. Autophagic vesicle formation in the heart ventricle is increased during zebrafish cardiac regeneration.
Pdf a chemical biology approach to myocardial regeneration. Review getting to the heart of regeneration in zebra. There is a long history of research in amphibian heart regeneration 9. Here, we have established a heart infarct model in zebrafish. The regenerative capacity of zebrafish reverses cardiac failure. These phenomena indicate that h 2 o 2 may play a positive role in repair of aki. Myocardial polyploidization creates a barrier to heart. Several nonmammalian vertebrates, including zebrafish, possess the. In vivo cardiac reprogramming contributes to zebrafish heart regeneration article pdf available in nature 4987455 june 20 with 315 reads how we measure reads. Kp split channel k,l,n,o or merged m,p confocal scans of dissociated. Our data show that the migration of cms into the injury site is regulated independently of proliferation, and that coordination of both processes is essential for heart regeneration. Transient regenerative potential of the neonatal mouse heart.
The most significant risk factors associated with the development of heart diseases include genetic and environmental factors such as hypertension, high blood cholesterol levels, diabetes, smoking, and obesity. Myocardial polyploidization creates a barrier to heart regeneration in. The study of zebrafish as a leading model organism for developmental biology is rapidly expanding. During heart regeneration in the zebrafish, fibrotic. However, due to the lack of a suitable infarct model, it is not known how these animals respond to myocardial infarction. Adult mammalian hearts lack any appreciable capacity to regenerate.
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