title: Ror2 signaling is required for local upregulation of GDF6 and activation of BMP signaling at the neural plate border.
abstract: The receptor tyrosine kinase Ror2 is a major Wnt receptor that activates β-catenin-independent signaling and plays a conserved role in the regulation of convergent extension movements and planar cell polarity in vertebrates. Mutations in the ROR2 gene cause recessive Robinow syndrome in humans, a short-limbed dwarfism associated with craniofacial malformations. Here, we show that Ror2 is required for local upregulation of gdf6 at the neural plate border in Xenopus embryos. Ror2 morphant embryos fail to upregulate neural plate border genes and show defects in the induction of neural crest cell fate. These embryos lack the spatially restricted activation of BMP signaling at the neural plate border at early neurula stages, which is required for neural crest induction. Ror2-dependent planar cell polarity signaling is required in the dorsolateral marginal zone during gastrulation indirectly to upregulate the BMP ligand Gdf6 at the neural plate border and Gdf6 is sufficient to rescue neural plate border specification in Ror2 morphant embryos. Thereby, Ror2 links Wnt/planar cell polarity signaling to BMP signaling in neural plate border specification and neural crest induction.
authors: Biology Department, Developmental Biology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen 91058, Germany.
authors: Carolin
authors: C
authors: Schille
authors: Department of Medical Statistics, University Medical Center Göttingen, Göttingen 37073, Germany.
authors: Michaela
authors: M
authors: Bayerlová
authors: Department of Medical Statistics, University Medical Center Göttingen, Göttingen 37073, Germany Department of Hematology/Medical Oncology, University Medical Center Göttingen, Göttingen 37099, Germany.
authors: Annalen
authors: 0000-0001-5809-9507
authors: A
authors: Bleckmann
authors: Biology Department, Developmental Biology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen 91058, Germany alexandra.schambony@fau.de.
authors: Alexandra
authors: 0000-0001-8771-5487
authors: A
authors: Schambony
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D055431:Growth Differentiation Factor 6 / Q000235:genetics / Q000378:metabolism*; D009432:Neural Crest / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D054258:Neural Plate / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014982:Xenopus laevis / Q000196:embryology / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; D055431:Growth Differentiation Factor 6; D057050:Receptor Tyrosine Kinase-like Orphan Receptors
keywords: BMP; Gdf6; Neural crest; Neural plate border; Ror2; Wnt