Browsing by Subject "Heart, Embryology"
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Item GATA Co-Factors : Collaborators in Cardiac Development, Conspirators in Cardiac Disease(2005-05-03) Kathiriya, Irfan S.; Srivastava, DeepakDisruption of fetal gene expression during cardiac development can result in congenital heart defects (CHDs), the most common developmental anomaly in humans and the leading non-infectious cause of death in newborns. The reactivation of fetal gene expression during cardiac hypertrophy in the adult is an adaptive response to pressure or volume overloads, but can lead to impaired cardiac function. Gata4, a member of a family of zinc-finger transcription factors, has been implicated as a key regulator of fetal cardiac gene expression during cardiac development and cardiac hypertrophy. This thesis work presents two novel transcriptional complexes likely found in these settings, one that cooperates to activate GATA-dependent transactivation and one that represses it.Item An Illustrative Approach to Understanding the Developmental Processes of Atrial and Ventricular Septation of the Heart During Embryogenesis and How Errors in These Processes Lead to Congenital Septal Heart Defects(2006-05-16) Suehs, Jennifer Angelo; Calver, Lewis E.The main objective of this thesis project is to visually communicate, through the use of two-dimensional animations, the normal developmental processes of atrial and ventricular septation, as well as the abnormal development of these processes that result in both atrial and ventricular septal defects. The use of animation, as opposed to two-dimensional illustrations, will possibly increase understanding of these subjects and lead to advances in the treatment and therapy of cardiovascular disease, specifically heart defects, in children, eventually leading to advances in the treatment of heart disease in adults. Five separate animations were created and evaluated by an audience knowledgeable in the field of cardiovascular research and development. This thesis describes the current need for animations of this subject matter, documenting the available resources already found in the field, and describing the background, research, project design, and technical implementation of the design process used to create the final animations.Item Transcriptional Profiling of Early Cardiac Development(2005-08-11) Masino, Amanda M.; Garry, Daniel J.Cardiogenesis is an intricate process that spans nearly the entire developmental history of the mammal. A thorough comprehension of the molecular interactions that direct cardiac development will improve our ability to understand and treat cardiovascular diseases. The earliest stages of heart development are of particular interest because it is during these stages that patterning of cardiac structure appears critical. Traditionally, studies of these early developmental processes have been conducted on chicken, fish, or frog embryos due to ease of manipulation. More recently, however, the wide availability of tools designed to manipulate and isolate cell populations in the murine embryo, together with the advent of technologies for studying gene expression at the transcriptome level, have allowed for detailed study of these events in mammalian systems. I applied transgenic labeling and flow cytometry to isolate cardiac cell populations from early mouse embryos. Transcriptome analysis of these cell populations allowed me to characterize unique gene expression patterns and identify novel genetic pathways relevant to cardiac development. I undertook three interrelated studies. First, I completed a survey of the transcriptome of the developing heart at the cardiac crescent, linear heart tube, and looped heart tube stages to describe molecular signatures in the developing heart. I defined gene expression patterns unique to the cardiac crescent and looped heart, and identified novel markers of the developing heart. The second study focused on defining the transcriptional network of a key cardiac regulator, Nkx2.5. I identified transcripts misexpressed during the early development of Nkx2.5 null embryos, including the Nkx2.5 transcriptional targets ETSrelated transcription factor 71 and vascular cell adhesion molecule. Lastly, I characterized Nkx2.5-dependent left-right patterning in the cardiac crescent that revealed early specification of chamber myocardial lineages. In conclusion, these studies have elucidated the molecular profile of the developing heart and provided novel insights into the earliest stages of cardiac development.