The Role of Cell Tracing and Fate Mapping Experiments in Cardiac Outflow Tract Development, New Opportunities through Emerging Technologies

Whilst knowledge regarding the pathophysiology of congenital heart disease (CHDs) has advanced greatly in recent years, the underlying developmental processes affecting the cardiac outflow tract (OFT) such as bicuspid aortic valve, tetralogy of Fallot and transposition of the great arteries remain poorly understood. Common among CHDs affecting the OFT, is a large variation in disease phenotypes. Even though the different cell lineages contributing to OFT development have been studied for many decades, it remains challenging to relate cell lineage dynamics to the morphologic variation observed in OFT pathologies. We postulate that the variation observed in cellular contribution in these congenital heart diseases might be related to underlying cell lineage dynamics of which little is known. We believe this gap in knowledge is mainly the result of technical limitations in experimental methods used for cell lineage analysis. The aim of this review is to provide an overview of historical fate mapping and cell tracing techniques used to study OFT development and introduce emerging technologies which provide new opportunities that will aid our understanding of the cellular dynamics underlying OFT pathology.