Fetal exposure to the mood-stabilizing drug lithium causes heart and neural tube defects by unknown mechanisms. Here, Mingda Han, Maria Serrano, Rosana Lastra-Vicente and colleagues find that folic acid prevents lithium-induced changes to the Wnt–β-catenin signaling pathway in chick and mouse embryos. They show that lithium-induced defects are similar to those associated with elevated plasma homocysteine, which results from insufficient dietary folic acid. Both lithium and homocysteine suppress expression of the Wnt-regulated genes Hex and Isl1. Folic acid protects against this disruption of Wnt–β-catenin signaling during heart development and ameliorates the cardiac defects associated with homocysteine or lithium exposure.
