Presenter: Thomas Forman
Faculty Mentor: Fernanda M. Bosada, Kryn Stankunas
Presentation Type: Poster 62
Primary Research Area: Science
Major: Biology, Human Physiology
Funding Source: Huestis-McLean Memorial Scholarship Recipient, $450; Apex Scholarship, University of Oregon, $1000 per term
Congenital valve disease affects at least two percent of the world’s population, a remarkable frequency that underlines the urgent need to understand the etiology of these common birth defects. These underlying abnormalities may originate from disruption of embryonic valve development. Primordial heart valves proceed through complex signaling events to form thin, elongated leaflets/cusps. However, the roles of many of these signaling pathways in valve development remain incompletely understood. Previous research indicates that Receptor Tyrosine Kinase (RTK) signaling, commonly involved in cell proliferation, is activated during valve mesenchyme expansion. We found that Lrig1, an RTK negative regulator, is dynamically expressed in the valves throughout development. We observed high expression in the endocardium of the atrioventricular canal (AVC) during the first steps of valve development. During valve mesenchyme expansion and elongation, we detected Lrig1 at the distal end of both the AVC and semilunar (SL) valves. Using a transgenic mouse line to knock out Lrig1 function, we demonstrated that homozygous Lrig1 embryos have hypertrophic AVC valves, although we observed no such defect in the SL valves. Interestingly, mutant AVC valves are not overproliferative at 13.5 days post-fertilization. We hypothesize that Lrig1 negatively regulates endocardial-to-mesenchymal transformation (EMT) in early valve development. Fate-mapping of Lrig1+ cells will further elucidate the roles of Lrig1. Our findings are the first ever to describe a function for Lrig1 in the heart valves.