Determining roles of Wnt signaling in mammalian heart valve development

Presenter: Andrew Mckay, Biology

Heart defects occur in 2% of live births, and of these, valve defects are the most common. By studying normal heart valve development we hope to find the genetic causes of these defects. Our primary question is: what signals direct the remodeling of embryonic heart valves into thin, elongated leaflets? We hypothesize that local Wnt signals direct heart valve remodeling by regulating cell proliferation and morphogenesis through activation of the NFATc1 transcription factor. To accomplish this, we use transgenic mice that allow us to block Wnt signaling during narrow time windows of embryogenesis. We inject transgenic mice with doxycycline, a molecule that causes the transgenes to temporarily express the Wnt antagonist Dkk-1 and inhibit Wnt signaling in particular cell types. I helped determined which of three transgenic lines best inhibits Wnt signaling and produces the most consistent and robust phenotype for valve defects. This line will be used for future experiments in which we will stain the sections for various cell type markers, indicators of proliferation, and localization of the transcription factor NFATc1. We will then use these results to determine if Wnt signaling affects cell proliferation and NFATc1 localization in targeted cell types in the developing valve.