title: Planar cell polarity defects and defective Vangl2 trafficking in mutants for the COPII gene Sec24b.
abstract: Among the cellular properties that are essential for the organization of tissues during animal development, the importance of cell polarity in the plane of epithelial sheets has become increasingly clear in the past decades. Planar cell polarity (PCP) signaling in vertebrates has indispensable roles in many aspects of their development, in particular, controlling alignment of various types of epithelial cells. Disrupted PCP has been linked to developmental defects in animals and to human pathology. Neural tube closure defects (NTD) and disorganization of the mechanosensory cells of the organ of Corti are commonly known consequences of disturbed PCP signaling in mammals. We report here a typical PCP phenotype in a mouse mutant for the Sec24b gene, including the severe NTD craniorachischisis, abnormal arrangement of outflow tract vessels and disturbed development of the cochlea. In addition, we observed genetic interaction between Sec24b and the known PCP gene, scribble. Sec24b is a component of the COPII coat protein complex that is part of the endoplasmic reticulum (ER)-derived transport vesicles. Sec24 isoforms are thought to be directly involved in cargo selection, and we present evidence that Sec24b deficiency specifically affects transport of the PCP core protein Vangl2, based on experiments in embryos and in cultured primary cells.
authors.affiliation: Hubrecht Institute, KNAW & University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands. c.wansleeben@hubrecht.eu
authors.forename: Carolien
authors.initials: C
authors.lastname: Wansleeben
authors.forename: Harma
authors.initials: H
authors.lastname: Feitsma
authors.forename: Mireille
authors.initials: M
authors.lastname: Montcouquiol
authors.forename: Carla
authors.initials: C
authors.lastname: Kroon
authors.forename: Edwin
authors.initials: E
authors.lastname: Cuppen
authors.forename: Frits
authors.initials: F
authors.lastname: Meijlink
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000002:abnormalities; D016764:Cell Polarity; D002478:Cells, Cultured; D003051:Cochlea / Q000002:abnormalities / Q000033:anatomy & histology / Q000196:embryology; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000033:anatomy & histology / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D006330:Heart Defects, Congenital; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009436:Neural Tube Defects / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D033921:Vesicular Transport Proteins; C431577:Ltap protein, mouse; C530639:SEC24B protein, human; C548501:SEC24b protein, mouse; C508433:scrib protein, mouse