Neogenin and RGMa control neural tube closure and neuroepithelial morphology by regulating cell polarity

Kee, Nigel, Wilson, Nicole, De Vries, Melissa, Bradford, DanaKai, Key, Brian and Cooper, Helen M. (2008) Neogenin and RGMa control neural tube closure and neuroepithelial morphology by regulating cell polarity. The Journal of Neuroscience, 28 48: 12643-12653. doi:10.1523/JNEUROSCI.4265-08.2008

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Author Kee, Nigel
Wilson, Nicole
De Vries, Melissa
Bradford, DanaKai
Key, Brian
Cooper, Helen M.
Title Neogenin and RGMa control neural tube closure and neuroepithelial morphology by regulating cell polarity
Journal name The Journal of Neuroscience   Check publisher's open access policy
ISSN 0270-6474
Publication date 2008-11-26
Year available 2008
Sub-type Article (original research)
DOI 10.1523/JNEUROSCI.4265-08.2008
Open Access Status File (Publisher version)
Volume 28
Issue 48
Start page 12643
End page 12653
Total pages 11
Place of publication New York, U.S.A.
Publisher Society for Neuroscience
Collection year 2009
Language eng
Subject C1
110902 Cellular Nervous System
920111 Nervous System and Disorders
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. Copyright ©2008 Society for Neuroscience
Keyword Neogenin
Cell polarity
Neural tube
Q-Index Code C1
Q-Index Status Confirmed Code

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Created: Thu, 12 Mar 2009, 15:37:23 EST by Debra McMurtrie on behalf of Queensland Brain Institute