Developmental consequences of abnormal folate transport during murine heart morphogenesis. Academic Article uri icon


  • BACKGROUND: Folic acid is essential for the synthesis of nucleotides and methyl transfer reactions. Folic acid-binding protein one (Folbp1) is the primary mediator of folic acid transport into murine cells. Folbp1 knockout mouse embryos die in utero with multiple malformations, including severe congenital heart defects (CHDs). Although maternal folate supplementation is believed to prevent human conotruncal heart defects, its precise role during cardiac morphogenesis remains unclear. In this study, we examined the role of folic acid on the phenotypic expression of heart defects in Folbp1 mice, mindful of the importance of neural crest cells to the formation of the conotruncus. METHODS: To determine if the Folbp1 gene participates in the commitment and differentiation of the cardiomyocytes, relative levels of dead and proliferating precursor cells in the heart were examined by flow cytometry, Western blot, and immunohistostaining. RESULTS: Our studies revealed that impaired folic acid transport results in extensive apoptosis-mediated cell death, which concentrated in the interventricular septum and truncus arteriosus, thus being anatomically restricted to the two regions of congenital heart defects. Together with a reduced proliferative capacity of the cardiomyocytes, the limited size of the available precursor cell pool may contribute to the observed cardiac defects. Notably, there is a substantial reduction in Pax-3 expression in the region of the presumptive migrating cardiac neural crest, suggesting that this cell population may be the most severely affected by the massive cell death. CONCLUSIONS: Our findings demonstrate for the first time a prominent role of the Folbp1 gene in mediating susceptibility to heart defects.

published proceedings

  • Birth Defects Res A Clin Mol Teratol

altmetric score

  • 3

author list (cited authors)

  • Tang, L. S., Wlodarczyk, B. J., Santillano, D. R., Miranda, R. C., & Finnell, R. H.

citation count

  • 63

complete list of authors

  • Tang, Louisa S||Wlodarczyk, Bogdan J||Santillano, Daniel R||Miranda, Rajesh C||Finnell, Richard H

publication date

  • July 2004