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Nat Commun 2024 Feb 22;151:1642. doi: 10.1038/s41467-024-45775-1.
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Noncanonical function of folate through folate receptor 1 during neural tube formation.

Balashova OA , Panoutsopoulos AA , Visina O , Selhub J , Knoepfler PS , Borodinsky LN .

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.

PubMed ID: 38388461
PMC ID: PMC10883926
Article link: Nat Commun
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: cbl cd2ap cdh3 eea1 folr1 pam sh3kbp1 ubb
GO keywords: neural tube formation [+]
Antibodies: Cbl Ab1 Cd2ap Ab1 Cdh3 Ab1 Eea1 Ab1
Morpholinos: cd2ap MO1 cd2ap MO2 folr1 MO1 folr1 MO3

Disease Ontology terms: neural tube defect
Phenotypes: Xla Wt + cd2ap MO1 (Fig. 7 b) [+]

Article Images: [+] show captions
References [+] :
Abdul-Wajid, T-type Calcium Channel Regulation of Neural Tube Closure and EphrinA/EPHA Expression. 2015, Pubmed, Xenbase