Due to the limited ability to mount a regenerative response in injured myocardium, cardiac dysfunction remains a key cause of morbidity and mortality. Coronary artery disease leads to myocardial infarction which results in fibrotic scarring, adverse remodeling, and heart failure.  In contrast to adult mice and humans, zebrafish retain the ability to undergo cardiomyocyte dedifferentiation and proliferation, ultimately stimulating cardiac regeneration following injury.  Deciphering the fundamental transcriptional networks shared in development and regeneration will fuel our ability to awaken endogenous reparative mechanisms. In zebrafish, embryonic cardiac transcriptional factors necessary for cardiogenesis, such as Nkx2.5, are galvanized following injury to stimulate cardiomyocyte production. Our ongoing studies investigate novel extracellular matrix proteins functioning downstream of Nkx2.5 to produce an extracellular milieu comprise of cardinal pro-regenerative proteins that can be harnessed to augment cell-based therapies for patients. We anticipate that our work will launch a novel paradigm highlighting the importance of embryonic ECM components in promoting epicardial and cardiomyocyte migration and tissue elasticity to enhance therapeutic strategies for patients.