Development of Diverse Cardiovascular Structures Derived from the Second Heart Field
- Author(s): Harmon, Andrew William
- Advisor(s): Nakano, Atsushi
- et al.
The heart is a specialized organ, responsible for distributing oxygenated blood through long distances of systemic vasculature. When fully formed it is composed of diverse cells types from several embryonic origins that must coordinate in order to function properly. During mammalian development the heart is the first organ to form and must become fully functional prior to the completion of organogenesis. The migratory cardiac progenitor population known as the second heart field is responsible for contributing not only additional cardiomyocytes to the nascent heart, but also endothelial and smooth muscle cells that will develop into specialized structures. Although the fates of the SHF have been well described, many potential mechanisms regulating the development of tissue derived from these progenitors remain to be examined.
This thesis is composed of five chapters including three original research articles (one of which has been published) and one that describes a recently established project. Chapter One will serve as an introduction and overview of heart development and cardiac-stem cell biology, including the cell fates of FHF and SHF progenitors. The contribution SHF-progenitors to the ascending aorta and the anatomical boundaries of the tissue derived from this source will be discussed in Chapter Two: "Nkx2-5 lineage tracing visualizes the distribution of second heart field-derived aortic smooth muscle". The role of the Serum Response Factor (SRF) co-factor Myocardin (Myocd) within the embryonic heart and SHF-derived smooth muscle will be described in Chapter Three: "The Role of Myocardin in Cardiogenesis and the Development SHF-derived Smooth Muscle". Finally, the role of inhibitory Smad (iSmad) proteins in the formation of SHF-derived cardiac structures will be discussed in Chapter Four: "The Role of Inhibitory Smads in the Embryonic Heart". The last chapter will discuss conclusions, implications of this work and future directions.