Activities of the Wnt-1 Class of Secreted Signaling Factors Are Antagonized by the Wnt-5A Class and by a Dominant Negative Cadherin in Early Xenopus Development

• Published in: The Journal of cell biology 1996-06, Vol.133 (5), p.1123-1137
• Main Authors: Torres, Monica A., Yang-Snyder, Julia A., Purcell, Susan M., DeMarais, Alyce A., McGrew, L. Lynn, Moon, Randall T.
• Format: Article
• Language: English
• Subjects: Animals; beta Catenin; Cadherins; Cadherins - physiology; Calcium-Calmodulin-Dependent Protein Kinases - pharmacology; Cell adhesion; Cell lines; Cells; Cellular biology; Cytoskeletal Proteins - pharmacology; Embryonic cells; Embryos; Epithelial cells; Female; Glycogen Synthase Kinase 3; Immunohistochemistry; In Situ Hybridization; Microinjections; Natural satellites; Neurons; Protein Sorting Signals - antagonists & inhibitors; Protein Sorting Signals - genetics; Protein Sorting Signals - physiology; Proto-Oncogene Proteins - antagonists & inhibitors; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - physiology; Reptiles & amphibians; RNA; RNA - administration & dosage; RNA - genetics; Signal Transduction; Trans-Activators; Wnt Proteins; Wnt-5a Protein; Wnt1 Protein; Xenopus; Xenopus laevis - embryology; Xenopus laevis - genetics; Xenopus laevis - physiology; Xenopus Proteins; Zebrafish Proteins
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.133.5.1123

When overexpressed in Xenopus embryos, Xwnt-1, -3A, -8, and -8b define a functional class of Wnts (the Wnt-1 class) that promotes duplication of the embryonic axis, whereas Xwnt-5A, -4, and -11 define a distinct class (the Wnt-5A class) that alters morphogenetic movements. Since some embryonic cells may be exposed to signals from both functional classes of Wnt during vertebrate development, this raises the question of how the signaling pathways of these classes of Wnts might interact. To address this issue, we coexpressed various Xwnts and components of the Wnt-1 class signaling pathway in developing Xenopus embryos. Members of the Xwnt-5A class antagonized the ability of ectopic Wnt-1 class to induce goosecoid expression and a secondary axis. Interestingly, the Wnt-5A class did not block goosecoid expression or axis induction in response to overexpression of cytoplasmic components of the Wnt-1 signaling pathway, β-catenin or a kinase-dead gsk-3, or to the unrelated secreted factor, BVg1. The ability of the Wnt-5A class to block responses to the Wnt-1 class may involve decreases in cell adhesion, since ectopic expression of Xwnt-5A leads to decreased Ca2+-dependent cell adhesion and the activity of Xwnt-5A to block Wnt-1 class signals is mimicked by a dominant negative N-cadherin. These data underscore the importance of cell adhesion in modulating the responses of embryonic cells to signaling molecules and suggest that the Wnt-5A functional class of signaling factors can interact with the Wnt-1 class in an antagonistic manner.