Deficiency of the Wnt receptor Ryk causes multiple cardiac and outflow tract defects. (4th March 2018)

• Record Type: Journal Article
• Authors: Kugathasan, Kumudhini; Halford, Michael M.; Farlie, Peter G.; Bates, Damien; Smith, Darrin P.; Zhang, You Fang; Roy, James P.; Macheda, Maria L.; Zhang, Dong; Wilkinson, James L.; Kirby, Margaret L.; Newgreen, Donald F.; Stacker, Steven A.
• Is Part Of: Growth factors. Volume 36:Number 1/2(2018)
• Page Start: 58
• Page End: 68
• Publication Date: 2018-03-04
• Subjects: Cardiovascular development -- growth factor receptor -- heart defects -- Ryk -- Wnt signalling; Growth factors -- Periodicals; Physiology -- Periodicals; 611
• DOI: 10.1080/08977194.2018.1491848
• Languages: English
• ISSNs: 0897-7194

Abstract

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.