Spatial and temporal expression of folate‐binding protein 1 (Fbp1) is closely associated with anterior neural tube closure in mice

Abstract

Periconceptional folate supplementation is widely believed to have significant preventive effects on the production of neural tube defects. Folate-binding protein 1 (FBP1) is one of the membrane proteins that mediate cellular uptake of folate. Although recent studies suggest that Fbp1 is essential for neural tube closure, the pattern of Fbp1 expression in embryonic tissues has not been examined in detail. To elucidate how Fbp1 contributes to neural tube closure, we examined the spatial and temporal expression patterns of Fbp1 in the developing neural folds and tube of mouse embryos by in situ hybridization. Fbp1 showed a distinct expression pattern in the neural folds, which preceded initiation of neural tube closure at the cervical region and the prosencephalic/mesencephalic boundary.

High‐affinity folate receptor in cardiac neural crest migration: A gene knockdown model using siRNA

“…To confirm that these results were consistent with the true distribution of Folr1 at the time of neural crest formation/migration, we used the public domain morphometric analysis system NIH Image to test the distribution of anti-FOLR1 antibody in the HH stage 17 embryo. The results showed that 72% of the labeling for FOLR-positive cells were in the neural tube and 18% was in the neural crest, supporting further the probability that the qPCR-detected decline in Folr1 reflected an siRNA knockdown effect specific to these regions; and confirming earlier reports on the spatial distribution of the folate receptor (Saitsu et al, 2003;Sato et al, 2008).…”

“…Therefore, we designed experiments to assess the role of the avian homolog of Folr1 during neural crest formation. We determined that the folate receptor gene Folr1 was highly expressed in the avian model in the neural crest and neural tube during neurulation, consistent with the results shown by Saitsu et al (2003) in the mammalian embryo during similar stages of development. Subsequently, we inserted by means of electroporation an short-interfering RNA (siRNA) directly into the neural tube at the site of formation of the premigratory cardiac neural crest.…”

“…Furthermore, Saitsu et al (2003) demonstrated that the expression of the folate receptor Folbp1 (also called Folr1, which is homologous with human Folr1 [FRalpha] and avian Folr1) was expressed at high levels in the dorsal neural tube during neural crest formation, indicating its potential role in neural crest development. These data, taken together with the results summarized above, led us to hypothesize that conotruncal heart defects that result from reduced availability of folate or reduced folate transport may occur because of an effect upon the cardiac neural crest and that reduced expression of the folate receptor specific to the cardiac neural crest would have an adverse effect upon its ability to support pharyngeal arch and conotruncal development.…”

“…Among these, the high-affinity receptor coded by the gene Folr1 is associated with high mitotic rates, e.g., in cancer cells (Hao et al, 2007) or with the dynamic growth processes during embryonic development (Saitsu et al, 2003;Sato et al, 2008), and appears to be the key to receptor-mediated endocytosis of folate during early embryonic development. Therefore, we designed experiments to assess the role of the avian homolog of Folr1 during neural crest formation.…”

Preconceptional folic acid supplementation in Japan

“…by 30–70% (Laurence et al 1981; Smithells et al 1983; Mulinare et al 1988; Mills et al 1989; Milunsky et al 1989; MRC Vitamin Study Research Group 1991; Saitsu et al 2003), leading to an international consensus on the importance of preconceptional FA supplementation. In Japan, despite the efforts of JSOG and JAOG, preconceptional FA supplementation was not universally accepted.…”