Noncanonical function of folate through folate receptor 1 during neural tube formation

Olga A. Balashova (), Alexios A. Panoutsopoulos, Olesya Visina, Jacob Selhub, Paul S. Knoepfler and Laura N. Borodinsky ()
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Olga A. Balashova: University of California Davis, School of Medicine
Alexios A. Panoutsopoulos: University of California Davis, School of Medicine
Olesya Visina: University of California Davis, School of Medicine
Jacob Selhub: Tufts–USDA Human Nutrition Research Center on Aging
Paul S. Knoepfler: University of California Davis, School of Medicine
Laura N. Borodinsky: University of California Davis, School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Folate supplementation reduces the occurrence of neural tube defects (NTDs), birth defects consisting in the failure of the neural tube to form and close. The mechanisms underlying NTDs and their prevention by folate remain unclear. Here we show that folate receptor 1 (FOLR1) is necessary for the formation of neural tube-like structures in human-cell derived neural organoids. FOLR1 knockdown in neural organoids and in Xenopus laevis embryos leads to NTDs that are rescued by pteroate, a folate precursor that is unable to participate in metabolism. We demonstrate that FOLR1 interacts with and opposes the function of CD2-associated protein, molecule essential for apical endocytosis and turnover of C-cadherin in neural plate cells. In addition, folates increase Ca2+ transient frequency, suggesting that folate and FOLR1 signal intracellularly to regulate neural plate folding. This study identifies a mechanism of action of folate distinct from its vitamin function during neural tube formation.

Date: 2024
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DOI: 10.1038/s41467-024-45775-1

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