Modeling anterior development in mice: Diet as modulator of risk for neural tube defects


  • Claudia Kappen

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    • Claudia Kappen holds the Peggy M. Pennington Cole Endowed Chair in Maternal Biology at the Pennington Biomedical Research Center/Louisiana State University System in Baton Rouge, LA. After receiving her Ph.D. degree in Molecular Genetics from the University of Cologne, Germany, she trained in Developmental Genetics at Yale University. She previously held faculty appointments at Mayo Clinic Scottsdale, AZ and the University of Nebraska Medical Center in Omaha, NE. Her research interests include the role of Hox genes in skeletal patterning, mechanisms of gene regulation, and the effects of maternal nutrition and metabolic disease in embryonic development.

Correspondence to: Claudia Kappen, Dr. rer. nat., Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808. E-mail:


Head morphogenesis is a complex process that is controlled by multiple signaling centers. The most common defects of cranial development are craniofacial defects, such as cleft lip and cleft palate, and neural tube defects, such as anencephaly and encephalocoele in humans. More than 400 genes that contribute to proper neural tube closure have been identified in experimental animals, but only very few causative gene mutations have been identified in humans, supporting the notion that environmental influences are critical. The intrauterine environment is influenced by maternal nutrition, and hence, maternal diet can modulate the risk for cranial and neural tube defects. This article reviews recent progress toward a better understanding of nutrients during pregnancy, with particular focus on mouse models for defective neural tube closure. At least four major patterns of nutrient responses are apparent, suggesting that multiple pathways are involved in the response, and likely in the underlying pathogenesis of the defects. Folic acid has been the most widely studied nutrient, and the diverse responses of the mouse models to folic acid supplementation indicate that folic acid is not universally beneficial, but that the effect is dependent on genetic configuration. If this is the case for other nutrients as well, efforts to prevent neural tube defects with nutritional supplementation may need to become more specifically targeted than previously appreciated. Mouse models are indispensable for a better understanding of nutrient–gene interactions in normal pregnancies, as well as in those affected by metabolic diseases, such as diabetes and obesity. © 2013 Wiley Periodicals, Inc.