Deficiency of the Wnt receptor Ryk causes multiple cardiac and outflow tract defects

AbstractRyk is a member of the receptor tyrosine kinase(RTK) family of proteins that control and regulate cellular processes. It is distinguished by binding Wnt ligands and having no detectable intrinsic protein tyrosine kinaseactivity suggesting Ryk is a pseudokinase. Here, we show an essential role for Ryk in directing morphogenetic events required for normal cardiac development through the examination of Ryk-deficient mice. We employed vascular corrosion casting, vascular perfusion with contrast dye, and immunohistochemistry to characterize cardiovascular and pharyngealdefects in Ryk−/− embryos. Ryk−/− mice exhibit a variety of malformations of the heart and outflow tract that resemble human congenital heart defects. This included stenosis and interruption of the aortic arch, ventriculoarterial malalignment, ventricular septal defects and abnormal pharyngeal archartery remodelling. This study therefore defines a key intersection between a subset of growth factor receptors involved in planar cell po...