title: 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.
abstract: 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 (Du, S., S. Purcell, J. Christian, L. McGrew, and R. Moon. 1995. Mol. Cell. Biol. 15:2625-2634). Since come 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, beta-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.
authors.affiliation: Department of Pharmacology, University of Washington School of Medicine, Seattle, 98195-7350, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Torres
authors.forename: J A
authors.initials: JA
authors.lastname: Yang-Snyder
authors.forename: S M
authors.initials: SM
authors.lastname: Purcell
authors.forename: A A
authors.initials: AA
authors.lastname: DeMarais
authors.forename: L L
authors.initials: LL
authors.lastname: McGrew
authors.forename: R T
authors.initials: RT
authors.lastname: Moon
mesh_terms: D000818:Animals; D015820:Cadherins / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000494:pharmacology; D005260:Female; D038362:Glycogen Synthase Kinase 3; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008845:Microinjections; D021382:Protein Sorting Signals / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology*; D012313:RNA / Q000008:administration & dosage / Q000235:genetics; D015398:Signal Transduction; D015534:Trans-Activators; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051155:Wnt1 Protein; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000502:physiology*; D029961:Zebrafish Proteins; D051176:beta Catenin
chemical_list: C495266:CTNNB1 protein, Xenopus; D015820:Cadherins; D003598:Cytoskeletal Proteins; D021382:Protein Sorting Signals; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; C495249:WNT1 protein, Xenopus; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051155:Wnt1 Protein; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D012313:RNA; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3