2012 Sep-Oct;20(5):638-46. doi: 10.1111/j.1524-475X.2012.00814.x. 2021 Apr 26;13(4):236-259. doi: 10.4252/wjsc.v13.i4.236. The teleost heart is composed of a single atrium and a single ventricle. Itou J, Oishi I, Kawakami H, Glass TJ, Richter J, Johnson A, Lund TC, Kawakami Y. That’s good news for us, because not only do zebrafish and humans have the same major organs and tissues, we share more than 80% of the same genes associated with human disease. 2016 Mar 1;143(5):729-40. doi: 10.1242/dev.132910. For more than a decade, zebrafish heart regeneration was studied exclusively using ventricular resection as the injury model (Fig. Regeneration occurs through robust proliferation of cardiomyocytes localized at the leading epicardial edge of the new myocardium. Stem Cell Res. Understanding natural models of heart regeneration will bring us closer to answering the ultimate question: how can we stimulate myocardial regeneration in humans? In zebrafish heart, the injury leads to a comparable fibrotic response: the intra-ventricular mechanical forces decrease during myocardial regeneration, leading to a down regulation of collagen synthesis and, eventually to the removal of the scar (43). eCollection 2021. After treatment with the MEK inhibitor AZD6244 upon cardiac injury, the core members in MAPK/ERK signalling—mek and erk—demonstrate elevated expression, and these proteins are deposited at the injury site in zebrafish. Heart repair and regeneration: recent insights from zebrafish studies. Zhao L, Borikova AL, Ben-Yair R, Guner-Ataman B, MacRae CA, Lee RT, Burns CG, Burns CE. Front Cell Dev Biol. (A) Genetic lineage‐tracing experiments to determine the origin…, Dynamics of zebrafish heart regeneration.…, Dynamics of zebrafish heart regeneration. 2021 Apr 11;22(8):3945. doi: 10.3390/ijms22083945. Virtually all cardiomyocytes in uninjured hearts are labeled by GFP expression after treatment with 4‐hydroxytamoxifen (4‐OHT). Bethesda, MD 20894, Copyright Encouraging results from our laboratory 24 and others 15 showed the feasibility of monitoring zebrafish heart regeneration by the use of microelectrodes. However, no zebrafish model is available that mimics ischemic injury in mammalian heart. Accessibility Therefore, deciphering the mechanisms that underlie the zebrafish heart's endogenous regenerative capacity represents an exciting avenue to identify novel therapeutic strategies for inducing regeneration of the human heart. This process requires interaction with epicardial cells, endocardial cells, and vascular endothelial cells. 2021 Feb 25;9:616893. doi: 10.3389/fcell.2021.616893. Zebrafish heart regeneration occurs over a 2-mo period [ 8 ]. Accessibility Epub 2014 Jan 13. dpi, days post‐injury; ECM, extracellular matrix; EP, epicardium; PVC, perivascular cell. Epub 2012 Oct 3. Science. R01 HL127067/HL/NHLBI NIH HHS/United States, R35 HL135831/HL/NHLBI NIH HHS/United States, Ablain, J. , Durand, E. M. , Yang, S. , Zhou, Y. , & Zon, L. I. Please enable it to take advantage of the complete set of features! Correlative evidence suggests that polyploidization of heart muscle, which occurs naturally in post-natal mammals, creates a barrier to heart regeneration. Myofibroblasts appear in the injury zone and there is an accumulation of extracellular matrix. CHLA researchers discover a mechanism of heart regeneration in zebrafish. (A) Schematic representation of the anatomical position of the heart in the adult zebrafish. doi: 10.1016/j.devcel.2018.01.021. (B) A population of subepicardial cardiomyocytes activates regulatory sequences of, Dynamics of zebrafish heart regeneration. 2021 May 5. doi: 10.1007/s00018-021-03831-9. Privacy, Help In contrast to a healthy heart, the infarcted ventricle shows a thinning of the affected wall, in which the cardiac muscle has been replaced by fibrotic tissue. (A) Schematic representation of a…, The zebrafish heart: anatomy, histology,…, The zebrafish heart: anatomy, histology, and injury paradigms. When the human heart is severely wounded — during, for example, a heart attack — it cannot regenerate the damaged muscle tissue. For simplicity, the presence of fibroblasts in the uninjured heart has been omitted. Journal of Cardiothoracic and Vascular Anesthesia, 23, 738–748. But, a tiny, striped, transparent fish outdoes them all — the zebrafish can repair and regenerate its heart, brain, retina, pancreas, spine, fins, and kidneys. doi: 10.1371/journal.pone.0251054. Zebrafish are extremely well-suited for the study of organ regeneration. Dev Dyn. Development. Wound Repair Regen. Clipboard, Search History, and several other advanced features are temporarily unavailable. In contrast, the zebrafish heart regenerates efficiently upon injury through robust myocardial proliferation. Methods Mol Biol. -, Aguirre, A. , Montserrat, N. , Zacchigna, S. , Nivet, E. , Hishida, T. , Krause, M. N. , …, Izpisua Belmonte, J. C. (2014). eCollection 2021. Epub 2014 Jul 19. Scar-Free Healing of Endometrium: Tissue-Specific Program of Stromal Cells and Its Induction by Soluble Factors Produced After Damage. Eremichev R, Kulebyakina M, Alexandrushkina N, Nimiritsky P, Basalova N, Grigorieva O, Egiazaryan M, Dyikanov D, Tkachuk V, Makarevich P. Front Cell Dev Biol. In this injury paradigm, a portion of the ventricle is removed, and regeneration is scored as complete regrowth of the lost tissue (Poss et … (B) Ventricular cryoinjury induces local tissue necrosis (gray) and apoptosis in all cell types around the injured region. 2021 Apr 1;10(1):11. doi: 10.1186/s13619-020-00072-2. pERK is also … Lien CL, Harrison MR, Tuan TL, Starnes VA. Transient reprogramming of postnatal cardiomyocytes to a dedifferentiated state. Keywords: J Cardiovasc Dev Dis. Notch signaling regulates cardiomyocyte proliferation during zebrafish heart regeneration. Representations of a region of the zebrafish heart in the absence of injury (A) or at different stages after cryoinjury (B−F). This site needs JavaScript to work properly. Aims the adult zebrafish heart regenerates spontaneously after injury and has been used to study the mechanisms of cardiac repair. LV, left ventricle; RV, right ventricle, The zebrafish heart: anatomy, histology, and injury paradigms. Ischemic myocardium eventually dies and is replaced by fibrotic tissue. This prevents the heart from contracting properly, impacting its ability to supply the body with fresh blood. Prevention and treatment information (HHS). The zebrafish has become a well-recognized model organism for studying embryonic development, organ function, and behavior, as well as organ regeneration including the heart (Poss et al. Tissue death triggers the recruitment of inflammatory cells and endocardial activation. Cell migration during heart regeneration in zebrafish. Introduction. (E) Cardiomyocyte genetic ablation causes diffuse loss of ∼60% of cardiomyocytes in the heart, while preserving the remaining cell types. Compared with newt and axolotl, a major advantage of the zebrafish model is the availability of a large number of transgenic or gene deletion strains, which are essential to … Compared to uninjured controls or to the contralateral wall, the regenerated wall shows a significant expansion of the cortical myocardium. The interaction of Notch and Wnt signaling pathways in vertebrate regeneration. In 2002, adult zebrafish heart regeneration was first reported (Poss et al., 2002). Unable to load your collection due to an error, Unable to load your delegates due to an error. 8600 Rockville Pike Thus, injury-induced cardiomyocyte proliferation in zebrafish can overcome scar formation, allowing cardiac muscle regeneration. Identification and requirements of enhancers that direct gene expression during zebrafish fin regeneration. -. In vivo activation of a conserved microRNA program induces mammalian heart regeneration. "We're interested in zebrafish because of their incredible capacity for regeneration," says Michael Harrison, PhD, a Research Associate in CHLA's Saban Research Institute. The Regulatory Role of Oxygen Metabolism in Exercise-Induced Cardiomyocyte Regeneration. eCollection 2021. The hearts of zebrafish with mutations in the Mps1 mitotic checkpoint kinase, a critical cell cycle regulator, failed to regenerate and formed scars. Science. We developed and characterized zebrafish cardiac injury induced by hypoxia/reoxygenation (H/R) and the regeneration that followed it. González-Rosa JM, Sharpe M, Field D, Soonpaa MH, Field LJ, Burns CE, Burns CG. The cortical myocardium is highly irrigated by coronary vessels. After amputation, a blood clot forms to seal the ventricle and stop bleeding. Epub 2012 Jul 20. (2015). (D) Cryoinjury induces local tissue necrosis (∼20% of the ventricle) and triggers apoptosis. The blood clot is replaced by a fibrin clot at 2 to 3 d postamputation (dpa). An adult zebrafish heart can fully regenerate after up to 20% volumetric loss by ventricular amputation, whereas a mammalian counterpart cannot sustain such an injury (15). … cardiomyocyte proliferation; heart regeneration; myocardial infarction; zebrafish. (F) In advanced stages of regeneration, the zebrafish myocardium appears completely restored. "We're interested in zebrafish because of their incredible capacity for regeneration," says Michael Harrison, Ph.D., a Research Associate in CHLA's Saban Research Institute. 2020;147:dev191262. Prevention and treatment information (HHS). (1978). This animation shows how zebrafish can rapidly heal wounds to the heart. Cell Stem Cell, 15, 589–604. 2016;1451:225-35. doi: 10.1007/978-1-4939-3771-4_15. How do different cell types interact to achieve organ regeneration? When blood flow is interrupted, a region of the myocardium becomes ischemic (brown shade). 8600 Rockville Pike When the zebrafish heart is damaged, the wound site is rapidly sealed with a fibrin clot that stems bleeding within seconds. Proc Natl Acad Sci U S A. Repair and reorganization of minced cardiac muscle in the adult newt (Notophthalmus viridescens). We summarize 15 years of research, with a special focus on recent developments from this fascinating field. Development. Over the decades that have followed, zebrafish have become a valuable tool to dissect embryogenesis. (B) Anatomical and histological differences between a healthy and an infarcted heart. Would you like email updates of new search results? 2021 Apr 15;9:664527. doi: 10.3389/fcell.2021.664527. -, Bader, D. , & Oberpriller, J. O. -, Augoustides, J. G. T. , & Riha, H. (2009). Studies over the past 13 years have identified processes and mechanisms of heart regeneration in zebrafish. Dev Cell. Recently, the cardiac surgical resection model in zebrafish,,,,, and neonatal mice has been successfully exploited to study myocardial regeneration. Zebrafish are native to river basins in and surrounding East India and were established as a laboratory model system first by Streisinger and colleagues during the 1970s, as a potential means to apply genetic analysis to vertebrate development [1,2]. Hemodynamic Forces Regulate Cardiac Regeneration-Responsive Enhancer Activity during Ventricle Regeneration. 2002 Dec 13;298(5601):2141-2. doi: 10.1126/science.1079821. This review provides a historical overview of adult zebrafish heart regeneration. Unable to load your collection due to an error, Unable to load your delegates due to an error, Causes and consequences of myocardial infarction in mammals. The Regulatory Role of Oxygen Metabolism in Exercise-Induced Cardiomyocyte Regeneration. Privacy, Help As a result, myocardial infarctions are responsible for approximately half of all cardiovascular related deaths. Kikuchi K, Holdway JE, Werdich AA, Anderson RM, Fang Y, Egnaczyk GF, Evans T, Macrae CA, Stainier DY, Poss KD. 2018 Feb 26;44(4):433-446.e7. 2021 Apr 15;9:664527. doi: 10.3389/fcell.2021.664527. Adult mammalian hearts have limited regeneration capacity in response to cardiac damage. Causes and consequences of myocardial infarction in mammals. -, Ahuja, P. , Perriard, E. , Perriard, J.‐C. Cardiac regeneration strategies: staying young at heart. Recent progress in heart failure treatment and heart transplantation. To better understand the molecular mechanisms of regeneration and explore the potential signalling pathways as therapeutic targets for heart attacks. 2014 Jan 28;111(4):1403-8. doi: 10.1073/pnas.1311705111. We discuss experimental findings that address fundamental questions of regeneration research. This fact has been cemented through several studies and is being used as the basis to fuel experiments aimed at finding ways to improve the regenerative capacity of the human heart. (C) Apex amputation removes ∼20% of the ventricle and leads to the formation of a fibrin clot. Please enable it to take advantage of the complete set of features! Nature. 2021 May 5;16(5):e0251054. The myocardium is divided into three distinctive populations: trabecular, primordial, and cortical. Ant, anterior; AT, atrium; BA, bulbus arteriosus; CM, cardiomyocyte; CV, coronary vasculature; Dor, dorsal; EC, endocardium; EP, epicardium; M, myocardium; Post, posterior; V, ventricle; Ven, ventral, Cellular origins of regenerated tissue. Cell Mol Life Sci. 2014 Nov;13(3 Pt B):542-55. doi: 10.1016/j.scr.2014.07.003. In contrast, the zebrafish heart regenerates efficiently upon injury through robust myocardial proliferation. These findings indicate that zebrafish will be useful for genetically dissecting the molecular mechanisms of cardiac regeneration. 2017;356:1035–9. This repair process, which is known as regeneration, has much in common with the complex developmental processes … These studies have demonstrated that in this experimental construct, there exists a regenerative potential within … Journal of Morphology, 155, 349–357. Humans, although inferior to zebrafish when it comes to heart regeneration, still possess some genes similar to those of zebrafish. In regenerated hearts, the new myocardium is GFP+, revealing that new muscle derives from the proliferation of preexisting cardiomyocytes (Jopling et al., 2010; Kikuchi et al., 2010). Here, we demonstrate histologically that zebrafish fully regenerate hearts within 2 months of 20% ventricular resection. Epub 2016 May 10. Primary contribution to zebrafish heart regeneration by gata4(+) cardiomyocytes. (C) During the first days after injury, epicardial and endocardial cells proliferate actively and cover the injured area, establishing a “regenerative scaffold.” Epicardial cells also undergo epithelial to mesenchymal transitions and invade the underlying myocardium. (A) Schematic representation of a human heart in which one of the coronary arteries is occluded by an atheromatous plaque (magnified area). See this image and copyright information in PMC. Myocardial Polyploidization Creates a Barrier to Heart Regeneration in Zebrafish. An international research group now shows that certain heart muscle cells play a … As the myocardium regenerates, the fibrotic tissue progressively disappears. 2010 Mar 25;464(7288):601-5. doi: 10.1038/nature08804. (D−E) Cardiomyocytes located in the wound edge proliferate and repopulate the injured area. 2016 Jul;245(7):774-87. doi: 10.1002/dvdy.24411. (A) Genetic lineage‐tracing experiments to determine the origin of regenerated myocardium during zebrafish heart regeneration. Careers. Clipboard, Search History, and several other advanced features are temporarily unavailable. eCollection 2021. Some animals, including the zebrafish, have a high capacity to regenerate tissues, allowing them to recovery fully after cardiac injury. Compared to other organs such as the liver, the adult human heart lacks the capacity to regenerate on a macroscopic scale after injury. Feng X, Travisano S, Pearson CA, Lien CL, Harrison MRM. Cell Regen. Migration of cardiomyocytes is essential for heart regeneration in zebrafish. Cardiovascular disease is the leading cause of death worldwide. Blood exits the heart through the bulbus arteriosus, an elastic, non‐contractile chamber composed of smooth muscle. A CRISPR/Cas9 vector system for tissue‐specific gene disruption in zebrafish. In a microarray-based gene profiling analysis of Müller glia-derived retinal stem cells in light-damaged retinas from adult zebrafish, we found that 2 genes required for regeneration of fin and heart tissues in zebrafish, hspd1 ( heat shock 60-kDa protein 1 ) and mps1 ( monopolar spindle 1 ), were up-regulated. Endothelial cells from the coronary vasculature are frequently surrounded by pericytes. FOIA However, a damaged zebrafish heart can recover most of its original shape, size, and function over time. What is the origin of regenerated muscle? (B) Histological organization of the adult zebrafish ventricle. After heart injury, pre‐existing cardiomyocytes dedifferentiate, enter the cell cycle, and repair the injured myocardium. Int J Mol Sci. The Lymphatic System in Zebrafish Heart Development, Regeneration and Disease Modeling. The human heart is a remarkable organ, but the zebrafish heart is even more remarkable because it can repair itself if it is damaged. 2021 Feb 19;8(2):21. doi: 10.3390/jcdd8020021. Sequential myofibrillar breakdown accompanies mitotic division of mammalian cardiomyocytes. Here, we move beyond a correlation by demonstrating that experimental polyploidization of zebrafish cardiomyocytes is sufficient to suppress their proliferative potential during regeneration. If scarring is extensive, heart failure can result. Advances in understanding the mechanism of zebrafish heart regeneration. Would you like email updates of new search results? Online ahead of print. Rheault-Henry M, White I, Grover D, Atoui R. World J Stem Cells. Although humans show minimal regenerative capability, zebrafish can regenerate their hearts through a mechanism whereby heart muscle cells (cardiomyocytes) revert to a … National Library of Medicine It is already known that zebrafish can flexibly regenerate their hearts after injury. , & Ehler, E. (2004). Kisby T, de Lázaro I, Stylianou M, Cossu G, Kostarelos K. PLoS One. Stem cell therapy for heart failure: Medical breakthrough, or dead end? (A) Schematic representation of the…, Cellular origins of regenerated tissue. “We’re interested in zebrafish because of their incredible capacity for regeneration,” says Michael Harrison, Ph.D., a Research Associate in CHLA’s Saban Research Institute. 2C). This site needs JavaScript to work properly. FOIA The hearts of zebrafish with mutations in the Mps1 mitotic checkpoint kinase, a critical cell cycle regulator, failed to regenerate and formed scars. Zebrafish possess enhanced capacity for heart regeneration. Studies over the past two decades have shown heart regeneration in zebrafish to be a dynamic process, choreographed by multiple cell types. Developmental Cell, 32, 756–764. Representations of a region of the zebrafish heart…, National Library of Medicine Thus, the zebrafish provides a genetically tractable model system in which to study the molecular mechanisms of heart regeneration. Building and re-building the heart by cardiomyocyte proliferation. Bethesda, MD 20894, Copyright Thus, injury-induced cardiomyocyte proliferation in zebrafish can overcome scar formation, allowing cardiac muscle regeneration. CAS Article Google Scholar Tzahor E, Poss KD. After heart injury, zebrafish cardiomyocytes can divide and the scar is replaced by new cardiac muscle. Development. The hearts of zebrafish with mutations in the Mps1 mitotic checkpoint kinase, a critical cell cycle regulator, failed to regenerate and formed scars. Journal of Cell Science, 117, 3295–3306. Int J Mol Sci. Cardiac muscle is covered externally by the epicardium and internally by the endocardium. Careers. How is regeneration controlled from a genetic and molecular perspective? Methodologies for Inducing Cardiac Injury and Assaying Regeneration in Adult Zebrafish. 2012 Nov;139(22):4133-42. doi: 10.1242/dev.079756. Therefore, deciphering the mechanisms that underlie the zebrafish heart's endogenous regenerative capacity represents an exciting avenue to identify novel therapeutic strategies for inducing regeneration of the human heart. Cardiac injury in mammals and amphibians typically leads to scarring, with minimal regeneration of heart muscle.
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