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

Abstract

Ryk 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 kinase activity 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 pharyngeal defects 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 arch artery remodelling. This study therefore defines a key intersection between a subset of growth factor receptors involved in planar cell polarity signalling, the Wnt family and mammalian cardiovascular development.

WNT/RYK signaling restricts goblet cell differentiation during lung development and repair

“…and in craniofacial morphogenesis (28,29). Recent studies reveal that RYK participates in mammary epithelial growth and branching morphogenesis (30) as well as in cardiac development (31). However, the potential role of RYK in lung development and homeostasis has not been studied.…”

Wnt lipidation: Roles in trafficking, modulation, and function

“…Receptor-like tyrosine kinase (Ryk) is a homolog of Drosophila Derailed and Caenorhabditis elegans Lin-18 and is involved in cell proliferation, migration, polarity, and development (Kugathasan et al, 2018). Ryk is a single-pass transmembrane protein composed of a HOSSEINI ET AL.…”

“…Receptor-like tyrosine kinase (Ryk) is a homolog of Drosophila Derailed and Caenorhabditis elegans Lin-18 and is involved in cell proliferation, migration, polarity, and development (Kugathasan et al, 2018). Ryk is a single-pass transmembrane protein composed of a noncatalytic tyrosine-kinase cytoplasmic domain and the extracellular WD domain that appears to function as a Wnt receptor or coreceptor, cooperating with the Fz receptor (Adamo et al, 2017).…”

RYK-mediated filopodial pathfinding facilitates midgut elongation

“…RYK is a less studied WNT5A receptor. Similar to Wnt5a-and Ror2-null embryos, Ryk −/− embryos have outgrowth defects in multiple organs (Halford et al, 2000;Kugathasan et al, 2018), but no gut phenotype has been described. Importantly, in mouse forebrain, RYK is responsible for establishing an appropriate axon trajectory guided by WNT5A (Keeble et al, 2006).…”