title: Folate receptor 1 is necessary for neural plate cell apical constriction duringXenopusneural tube formation.
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 introducesXenopus laevisas a model to determine the cellular and molecular mechanisms involved in folate action during neural tube formation. We show that knockdown of folate receptor 1 (Folr1; also known as FRα) impairs neural tube formation and leads to NTDs. Folr1 knockdown in neural plate cells only is necessary and sufficient to induce NTDs. Folr1-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 in which the folate receptor interacts with cell adhesion molecules, thus regulating the apical cell membrane remodeling and cytoskeletal dynamics necessary for neural plate folding. Further studies in this organism could unveil novel cellular and molecular events mediated by folate and lead to new ways of preventing NTDs.
authors.affiliation: 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.
authors.forename: Olga A
authors.initials: OA
authors.lastname: Balashova
authors.affiliation: 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.
authors.forename: Olesya
authors.initials: O
authors.lastname: Visina
authors.affiliation: 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 lnborodinsky@ucdavis.edu.
authors.forename: Laura N
authors.identifier: 0000-0003-2937-7023
authors.initials: LN
authors.lastname: Borodinsky
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D016764:Cell Polarity / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D058975:Folate Receptor 1 / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D055785:Gene Knockdown Techniques; D018390:Gene Targeting; D006801:Humans; D060172:Morpholinos / Q000494:pharmacology; D054258:Neural Plate / Q000166:cytology* / Q000378:metabolism*; D054259:Neural Tube / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D054261:Neurulation / Q000187:drug effects; D038081:Organogenesis / Q000187:drug effects; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000378:metabolism
chemical_list: D015820:Cadherins; D058975:Folate Receptor 1; D060172:Morpholinos; D029867:Xenopus Proteins
keywords: Folate receptor; Folic acid; Neural tube defects; Xenopus