Tracing the Endocardial Cell Lineage of Developing Heart Valves Using MADMMatter Pools?

Presenter : Amy Jones

Mentor : Kryn Stankunas

Major : Biology, Human Physiology

Poster 15

Heart valve development is a complex, multi-step process. During development, endocardial cushions form at specific locations in
the early heart tube. These cushions are populated by endocardial cells that delaminate in a process known as epithelial-mesenchymal transformation (EMT). In the mouse, EMT takes place between embryonic day 9.5-10.5. It is a vital process to understand since the heart valves are derived from this cardiac cushion tissue. Current models of cushion EMT suggest that a large number of endocardial cells undergo EMT. An alternative hypothesis is that only a few individual cells initially populate the cushions that then proliferate to expand cushion mesenchyme.To better understand how endocardial-derived cells contribute to heart valves, I am using a novel mouse genetic system termed MADM (mosaic analysis with double markers). MADM uses the Cre-lox system to permanently label specified cells by fluorescent protein expression. For my studies, I use the Tie2 promoter to direct Cre expression and instruct the MADM system to specifically trace the endocardial cell lineage. The low frequency by which labeled cells are generated allows me to exquisitely moni- tor contributions of clonally-related endocardial cells to developing valves. By gaining a complete understanding of the contribution of endothelial-lineage cells to developing valves, we can identify when embryonic heart malformations originate, supporting the development of therapeutics to prevent defective valves from progressing to a diseased state.

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