title: Controlled levels of canonical Wnt signaling are required for neural crest migration.
abstract: Canonical Wnt signaling plays a dominant role in the development of the neural crest (NC), a highly migratory cell population that generates a vast array of cell types. Canonical Wnt signaling is required for NC induction as well as differentiation, however its role in NC migration remains largely unknown. Analyzing nuclear localization of β-catenin as readout for canonical Wnt activity, we detect nuclear β-catenin in premigratory but not migratory Xenopus NC cells suggesting that canonical Wnt activity has to decrease to basal levels to enable NC migration. To define a possible function of canonical Wnt signaling in Xenopus NC migration, canonical Wnt signaling was modulated at different time points after NC induction. This was accomplished using either chemical modulators affecting β-catenin stability or inducible glucocorticoid fusion constructs of Lef/Tcf transcription factors. In vivo analysis of NC migration by whole mount in situ hybridization demonstrates that ectopic activation of canonical Wnt signaling inhibits cranial NC migration. Further, NC transplantation experiments confirm that this effect is tissue-autonomous. In addition, live-cell imaging in combination with biophysical data analysis of explanted NC cells confirms the in vivo findings and demonstrates that modulation of canonical Wnt signaling affects the ability of NC cells to perform single cell migration. Thus, our data support the hypothesis that canonical Wnt signaling needs to be tightly controlled to enable migration of NC cells.
authors.affiliation: Department of Biology, Molecular Embryology, Philipps-Universität Marburg, Karl-von-Frisch-Str. 8, 35043 Marburg, Germany.
authors.forename: Ewa
authors.initials: E
authors.lastname: Maj
authors.affiliation: Institute for Theoretical Physics, Georg August University Göttingen, Friedrich-Hund-Platz, 37077 Göttingen, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Künneke
authors.affiliation: Department of Biology, Molecular Embryology, Philipps-Universität Marburg, Karl-von-Frisch-Str. 8, 35043 Marburg, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Loresch
authors.affiliation: Department of Biology, Molecular Embryology, Philipps-Universität Marburg, Karl-von-Frisch-Str. 8, 35043 Marburg, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Grund
authors.affiliation: Department of Developmental Biochemistry, Georg August University Göttingen, Justus-von-Liebig-Weg 11, 37077 Göttingen, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Melchert
authors.affiliation: Department of Developmental Biochemistry, Georg August University Göttingen, Justus-von-Liebig-Weg 11, 37077 Göttingen, Germany.
authors.forename: Tomas
authors.initials: T
authors.lastname: Pieler
authors.affiliation: Institute for Mathematical Stochastics and Felix Bernstein Institute for Mathematical Statistics, Georg August University Göttingen, Goldschmidtstr. 7, 37077 Göttingen, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Aspelmeier
authors.affiliation: Department of Biology, Molecular Embryology, Philipps-Universität Marburg, Karl-von-Frisch-Str. 8, 35043 Marburg, Germany. Electronic address: borchers@uni-marburg.de.
authors.forename: Annette
authors.initials: A
authors.lastname: Borchers
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D017403:In Situ Hybridization; D007211:Indoles / Q000494:pharmacology; D009432:Neural Crest / Q000166:cytology*; D038081:Organogenesis / Q000502:physiology; D010091:Oximes / Q000494:pharmacology; D012886:Skull / Q000196:embryology; D051820:TCF Transcription Factors / Q000378:metabolism*; D058127:Transcription Factor 3 / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology*; D029867:Xenopus Proteins / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: C483321:6-bromoindirubin-3'-oxime; D007211:Indoles; D010091:Oximes; D051820:TCF Transcription Factors; C544917:Tcf3 protein, Xenopus; D058127:Transcription Factor 3; D051153:Wnt Proteins; D029867:Xenopus Proteins; D051176:beta Catenin
keywords: Canonical Wnt signaling; Cell migration; Neural crest; Xenopus