Transcriptional and Translational Regulation of Heart Development in Mammals
Ransom, Joshua Fuller
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The heart is the first organ to form in the embryo to support the growing need for oxygen and nutrients. To form correctly, this vital organ requires a high degree of regulation. Thus far, almost every known form of regulation that the mammalian cell has evolved is utilized in the proper development of the heart. Because the heart is so highly regulated, there are many steps at which a wrong turn can be made, leading to congenital cardiovascular malformations, which occur in one percent of all births and are the leading non-infectious cause of death in the first year of life. The majority of genes known to be involved in cardiogenesis in mammals are grouped at nodes which control many simultaneous aspects of differentiation, morphology, and heart size. This thesis work will discuss three separate lines of inquiry into cardiogenic nodes in mammalian heart development. The first deals with post-translational regulation of the Myocardin-dependent transcriptional node. The second story delves into the role of the Notch signaling pathway in human disease and how Notch regulates Myocardin and its downstream target gene, microRNA-1. The final account looks into regulation of protein translation through microRNAs in the heart with emphasis on microRNA-1-2.