Cardiac Regeneration in the Zebrafish Model System
This chapter reviews what is known about mechanisms of heart regeneration in zebrafish. In addition to addressing "how" regeneration occurs, it will touch on questions of "why." That is, why is the capacity for natural heart regeneration limited to nonmammalian species? Unlike mammals, zebrafish have the capacity to regenerate cardiac muscle removed by mechanical injury. They do so by stimulating the creation of new cardiomyocytes at the injury site, and by restricting scar formation. Research has essentially just begun to dissect the underlying mechanisms. Initial findings indicate that the regenerating heart establishes a field of cardiac progenitors, much like the embryonic heart field, as a source of new, proliferative cardiomyocytes. Regenerative cardiogenesis then proceeds in a wave of progenitor cell seeding, cardiomyocyte differentiation, and proliferation. Concomitantly, the epicardial cell layer that surrounds the myocardium proper responds to injury by expressing embryonic epicardial markers and proliferating. Then, in a process of epithelial-to-mesenchymal transition reminiscent of embryonic epicardial cells, the wound and regenerating muscle become populated by invading epicardial-derived cells. These epithelial-to-mesenchymal transition events, and the neovascularization that accompanies them, require the Fgf signaling pathway, ostensibly with Fgf ligands synthesized in injured/regenerating muscle recruiting epicardial-derived cells that express Fgf receptors. These events point to an intricate orchestration of different cardiac cell types to carry out regeneration in the injured zebrafish heart. © 2010 Elsevier Inc. All rights reserved.
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