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XB-ART-53082
Development. April 15, 2017; 144 (8): 1518-1530.

Folate receptor 1 is necessary for neural plate cell apical constriction during Xenopus neural tube formation.

Balashova OA , Visina O , Borodinsky LN .


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 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.

PubMed ID: 28255006
PMC ID: PMC5399658
Article link: Development.
Grant support: R01 NS073055 NINDS NIH HHS , R01 NS073055 NINDS NIH HHS

Genes referenced: cdh1 cdh3 ctnnb1 eea1 folr1 sox2 tubb

Antibodies referenced: Cdh1 Ab1 Cdh3 Ab1 Sox2 Ab6 Tubb Ab1 ctnnb1 Ab13
Morpholinos referenced: folr1 MO1 folr1 MO2

References:
, 1991, Pubmed[+]


Article Images: [+] show captions

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