AbstractCardiovascular diseases are a leading cause of mortality world-wide. The general approach to managing the disease burden is to reduce risk factors and to control symptoms. However, when a heart attack occurs and cardiomyocytes perish as a result, there currently is no feasible strategy to replace the lost cells and to cure the disease. Progress has been made to generate cardiomyocytes in vitro, but these cells fail to integrate and beat according to the rhythm set by the existing heart. Yet in the embryo there are cells that achieve this; the secondary heart field cells. These cells are added onto the primitive heart over a prolonged time during embryogenesis and follow the beat set by the existing cells. The challenge is to molecularly characterise these cells such that the recruitment and integration process can be recapitulated in a patient. Both the primary heart field cells for the primitive heart and the secondary heart field cells that are added on later arise from the embryonic head mesoderm. Previous studies showed that initially, the entire head mesoderm is cardiac competent. Yet eventually, cells from the head mesoderm also form non-cardiac tissues such as skeletal muscle. It is therefore important to determine the time window in which the head mesoderm is heart-competent as stepping stone towards further molecular analyses.
The chicken embryo is used as an established model for human heart development. Bone morphogenetic protein (BMP) are crucial for the induction of cardiogenesis and cardiomyocyte differentiation. BMP is loaded onto carrier beads and is implanted into the paraxial aspect of the head mesoderm that is fated to produce non-cardiogenic cell types. The experiment was conducted at several time points in development; embryos were analysed by in situ hybridisation for the expression of various cardiac and non-cardiac marker genes. It was found that the head mesoderm has full cardiac competence up to stages HH5/6 of development, which is 12 hours after the head mesoderm first formed at HH3/4. In the subsequent hours, cardiac competence declines as successively fewer cardiac markers respond to BMP. Instead, markers typical for head skeletal muscle precursors become activated, suggesting a shift from cardiac to myogenic competence. This suggest that the analysis of the molecular control and the underlying mechanism of the decline of cardiac competence has to focus onto the early head mesoderm.
|Date of Award||21 Feb 2023|
|Supervisor||Susanne Dietrich (Supervisor), Fiona Myers (Supervisor) & Frank Schubert (Supervisor)|