title: Neogenin and RGMa control neural tube closure and neuroepithelial morphology by regulating cell polarity.
abstract: In humans, neural tube closure defects occur in 1:1000 pregnancies. The design of new strategies for the prevention of such common defects would benefit from an improved understanding of the molecular events underlying neurulation. Neural fold elevation is a key morphological process that acts during neurulation to drive neural tube closure. However, to date, the molecular pathways underpinning neural fold elevation have not been elucidated. Here, we use morpholino knock-down technology to demonstrate that Repulsive Guidance Molecule (RGMa)-Neogenin interactions are essential for effective neural fold elevation during Xenopus neurulation and that loss of these molecules results in disrupted neural tube closure. We demonstrate that Neogenin and RGMa are required for establishing the morphology of deep layer cells in the neural plate throughout neurulation. We also show that loss of Neogenin severely disrupts the microtubule network within the deep layer cells suggesting that Neogenin-dependent microtubule organization within the deep cells is essential for radial intercalation with the overlying superficial cell layer, thereby driving neural fold elevation. In addition, we show that sustained Neogenin activity is also necessary for the establishment of the apicobasally polarized pseudostratified neuroepithelium of the neural tube. Therefore, our study identifies a novel signaling pathway essential for radial intercalation and epithelialization during neural fold elevation and neural tube morphogenesis.
authors.affiliation: Queensland Brain Institute, The University of Queensland, Queensland, Brisbane 4072, Australia.
authors.forename: Nigel
authors.initials: N
authors.lastname: Kee
authors.forename: Nicole
authors.initials: N
authors.lastname: Wilson
authors.forename: Melissa
authors.initials: M
authors.lastname: De Vries
authors.forename: DanaKai
authors.initials: D
authors.lastname: Bradford
authors.forename: Brian
authors.initials: B
authors.lastname: Key
authors.forename: Helen M
authors.initials: HM
authors.lastname: Cooper
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D016764:Cell Polarity / Q000235:genetics*; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D054259:Neural Tube / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D046569:Neuroepithelial Cells / Q000378:metabolism* / Q000473:pathology; D055495:Neurogenesis / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis; D015027:Zebrafish
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D029867:Xenopus Proteins; C091279:neogenin; C513829:rgma protein, Xenopus