EMBRYONIC FOLATE METABOLISM AND MOUSE NEURAL-TUBE DEFECTS

Folic acid prevents 70 percent of human neural tube defects (NTDs) but its mode of action is unclear. The deoxyuridine suppression test dete cts disturbance of folate metabolism in homozygous splotch (Pax3) mous e embryos that are developing NTDs in vitro. Excessive incorporation o f [H-3]thymidine in splotch embryos indicates a metabolic deficiency i n the supply of folate for the biosynthesis of pyrimidine. Exogenous f olic acid and thymidine both correct the biosynthetic defect and preve nt some NTDs in splotch homozygotes, whereas methionine has an exacerb ating effect. These data support a direct normalization of neurulation by folic acid in humans and suggest a metabolic basis for folate acti on.