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RESEARCH ARTICLE
Folate receptor alpha is necessary for neural plate cell apical constriction during Xenopus neural tube formation
Olga A. Balashova, Olesya Visina, Laura N. Borodinsky
Development 2017 : dev.137315 doi: 10.1242/dev.137315 Published 2 March 2017
Olga A. Balashova
Department of Physiology & Membrane Biology and Institute for Pediatric Regenerative Medicine, Shriners Hospital for Children, University of California Davis School of Medicine, Sacramento, CA 95817, USA
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Olesya Visina
Department of Physiology & Membrane Biology and Institute for Pediatric Regenerative Medicine, Shriners Hospital for Children, University of California Davis School of Medicine, Sacramento, CA 95817, USA
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Laura N. Borodinsky
Department of Physiology & Membrane Biology and Institute for Pediatric Regenerative Medicine, Shriners Hospital for Children, University of California Davis School of Medicine, Sacramento, CA 95817, USA
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  • ORCID record for Laura N. Borodinsky
  • For correspondence: lnborodinsky@ucdavis.edu
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Abstract

Folate supplementation prevents up to 70% of neural tube defects (NTDs), which result from a failure of neural tube closure during embryogenesis. The elucidation of the mechanisms underlying folate action has been challenging. This study introduces Xenopus laevis as a model to determine the cellular and molecular mechanisms involved in folate action during neural tube formation. We show that knockdown of folate receptor-α (FRα) impairs neural tube formation and leads to NTDs. FRα knockdown in neural plate cells only is necessary and sufficient to induce NTDs. FRα-deficient neural plate cells fail to constrict, resulting in widening of the neural plate midline and defective neural tube closure. Pharmacological inhibition of folate action by methotrexate during neurulation induces NTDs by inhibiting folate interaction with its uptake systems. Our findings support a model for folate receptor interacting with cell adhesion molecules, thus regulating apical cell membrane remodeling and cytoskeletal dynamics necessary for neural plate folding. Further studies in this organism may unveil novel cellular and molecular events mediated by folate and lead to new means for preventing NTDs.

  • Received March 7, 2016.
  • Accepted February 17, 2017.
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Keywords

  • Folic acid
  • neural tube defects
  • Xenopus
  • folate receptor

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Folate receptor alpha is necessary for neural plate cell apical constriction during Xenopus neural tube formation
Olga A. Balashova, Olesya Visina, Laura N. Borodinsky
Development 2017 : dev.137315 doi: 10.1242/dev.137315 Published 2 March 2017
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Folate receptor alpha is necessary for neural plate cell apical constriction during Xenopus neural tube formation
Olga A. Balashova, Olesya Visina, Laura N. Borodinsky
Development 2017 : dev.137315 doi: 10.1242/dev.137315 Published 2 March 2017

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