title: The involvement of PCP proteins in radial cell intercalations during Xenopus embryonic development.
abstract: The planar cell polarity (PCP) pathway orients cells in diverse epithelial tissues in Drosophila and vertebrate embryos and has been implicated in many human congenital defects and diseases, such as ciliopathies, polycystic kidney disease and malignant cancers. During vertebrate gastrulation and neurulation, PCP signaling is required for convergent extension movements, which are primarily driven by mediolateral cell intercalations, whereas the role for PCP signaling in radial cell intercalations has been unclear. In this study, we examine the function of the core PCP proteins Vangl2, Prickle3 (Pk3) and Disheveled in the ectodermal cells, which undergo radial intercalations during Xenopus gastrulation and neurulation. In the epidermis, multiciliated cell (MCC) progenitors originate in the inner layer, but subsequently migrate to the embryo surface during neurulation. We find that the Vangl2/Pk protein complexes are enriched at the apical domain of intercalating MCCs and are essential for the MCC intercalatory behavior. Addressing the underlying mechanism, we identified KIF13B, as a motor protein that binds Disheveled. KIF13B is required for MCC intercalation and acts synergistically with Vangl2 and Disheveled, indicating that it may mediate microtubule-dependent trafficking of PCP proteins necessary for cell shape regulation. In the neural plate, the Vangl2/Pk complexes were also concentrated near the outermost surface of deep layer cells, suggesting a general role for PCP in radial intercalation. Consistent with this hypothesis, the ectodermal tissues deficient in Vangl2 or Disheveled functions contained more cell layers than normal tissues. We propose that PCP signaling is essential for both mediolateral and radial cell intercalations during vertebrate morphogenesis. These expanded roles underscore the significance of vertebrate PCP proteins as factors contributing to a number of diseases, including neural tube defects, tumor metastases, and various genetic syndromes characterized by abnormal migratory cell behaviors.
authors.affiliation: Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Ossipova
authors.affiliation: Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Chih-Wen
authors.initials: CW
authors.lastname: Chu
authors.affiliation: Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Fillatre
authors.affiliation: Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Brott
authors.affiliation: Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Keiji
authors.initials: K
authors.lastname: Itoh
authors.affiliation: Department of Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: sergei.sokol@mssm.edu.
authors.forename: Sergei Y
authors.initials: SY
authors.lastname: Sokol
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology; D000818:Animals; D030801:Animals, Genetically Modified; D002465:Cell Movement; D016764:Cell Polarity / Q000235:genetics / Q000502:physiology*; D022081:Cell Surface Extensions / Q000235:genetics / Q000502:physiology; D002923:Cilia / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D000072261:Dishevelled Proteins; D004847:Epithelial Cells / Q000502:physiology; D054262:Gastrulation / Q000235:genetics / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000502:physiology; D060588:LIM Domain Proteins / Q000235:genetics / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D054261:Neurulation / Q000235:genetics / Q000502:physiology; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D029867:Xenopus Proteins / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D000072261:Dishevelled Proteins; D060588:LIM Domain Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; C491760:Vangl2 protein, Xenopus; D029867:Xenopus Proteins; C510818:prickle1 protein, Xenopus; D016547:Kinesins
keywords: Disheveled; Gastrulation; KIF13B; Multiciliated cells; Planar cell polarity; Prickle3; Radial intercalation; Vangl2; Xenopus