The cardiac repair response of Xenopus laevis tadpoles to KillerRed-induced oxidative stress
Abstract: The heart is an organ of vital importance and great fragility. In humans, damage to the heart leads to scarring, dysfunction, and heart failure. In contrast, amphibian hearts have heightened reparative abilities, and an understanding of how they accomplish this feat can lead to a greater knowledge of improving human heart health. We have developed a novel optogenetic model of heart disea... read morese in the Xenopus laevis tadpole, taking advantage of the unique ability of a genetically encoded photosensitizer, the KillerRed protein, to generate reactive oxygen species upon activation with green light. We show that KillerRed can be used to ablate tissues and developing organs in the X. laevis tadpole, and that when this method of damage is applied to the heart, it induces a phenotype mimicking cardiac stress in mammals. We demonstrate that partial dedifferentiation and proliferation of cardiomyocytes, mechanisms normally associated with cardiac regeneration, are activated in the X. laevis heart (a nonregenerative system) following KillerRed-induced damage, and that these mechanisms are regulated by different pathways than they are in organisms with fully regenerative hearts. Finally, we characterize the effects of alternate methods of activating KillerRed in the heart and show that activation by different light sources induces drastically different phenotypes. The data we present here show the unique nature of the Xenopus laevis cardiac response to oxidative stress, distinct from either mammals or organisms capable of full cardiac regeneration, and highlight this model system's importance in demonstrating an intermediate level of reparative and regenerative potential.
Thesis (Ph.D.)--Tufts University, 2018.
Submitted to the Dept. of Biology.
Advisor: Kelly McLaughlin.
Committee: Stephen Fuchs, Michael Levin, Harry Bernheim, and Catherine McCusker.
Keyword: Developmental biology.read less