Genetics of endocardial-myocardial interactions during zebrafish heart development

• Applicant: Professor Dr. Salim Seyfried
• Subject Area: Developmental Biology
• Term: since 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 177104192

The endocardium is a specialized endothelium lining the interior of the heart tube with important roles in cardiac development and physiology. Despite its importance for the correct functioning of the heart, the developmental origin of endocardial progenitor cells and the molecular mechanisms of endocardial cell fate specification have largely remained unresolved. This proposal aims at characterizing the molecular mechanisms of endocardial cell fate specification and at developing transgenic approaches to induce endocardium in the zebrafish embryo. This will allow us to address fundamental mechanistic and molecular questions related to endocardial biology, development, physiology, and to its interactions with myocardium. First, we will generate stable transgenic lines of zebrafish for the forced overexpression of candidate factors with a role in endocardial cell fate specification. In cell transplantation assays, we will then introduce cells from these transgenic lines into wild-type embryos and assess their contribution to the nascent endocardium. This approach will reveal molecular signatures required for inducing endocardial cell fate. In own preliminary work, we recently found that loss of the auxiliary Hedgehog receptor Lrp2b completely deletes endocardial tissue while the myocardium is still present. Here, we will further analyse its role and that of Hedgehog signaling in endocardial progenitor cell biology. Of particular interest will be the genetic hierarchy of Lrp2b and of Hedgehog signaling in relation to other regulators of endocardial cell fate specification. Taken together, these studies will provide important novel insights into the developmental origins of this unique vessel bed. The generation of transgenically-encoded constructs for the induction of endocardial cell fate will open novel avenues to functionally manipulate endocardial progenitor cells.

• DFG Programme: Research Grants