Grant: Travel Awards - Institute Community Support

Neural tube defects (NTDs) are a group of congenital malformation affecting the brain and spinal cord that occur when the neural tube fails to close during embryonic development. Although perinatal folic acid supplementation has reduced the risk of neural tube defects by 60-70%, they still remain the second most common birth defect with an incidence of 1 per 1000 live births. While both genetic and environmental factors are known to cause NTDs, how these factors mechanistically interfere with the normal events of neural tube closure remains poorly understood. The chick embryo is a suitable model in which to study neural tube closure because the tissue movements that lead to neural tube closure are identical to those that occur in the human embryo. I have shown that removal of multiple members of the claudin family of tight junction proteins from the chick embryo leads to open NTDs at the level of the brain, spinal cord and, in many cases, along the entire length of the embryo. This pleiotropic phenotype is similar to what is observed in humans, even when the disorder is caused by a single gene. I am using the chick embryo to investigate which of the morphogenetic events required for neural tube closure are regulated by claudins. I am also sequencing claudin genes in a human cohort with NTDs to identify mutations in claudin genes. This study will provide a better understanding of the mechanisms underlying normal neurulation and the interplay between genetic mutations and environmental events that lead to NTDs.