Abnormal Enteric Nervous System Organization and Gastrointestinal Motility in Mice With Valproic Acid-Induced Neural Tube Defects

BACKGROUND: Neural tube defects (NTDs) are a common congenital birth anomaly that can occur at either cranial levels, resulting in anencephaly, or spinal levels, resulting in spina bifida. Neurogenic bowel is a major cause of morbidity in patients affected by spina bifida, but it is unknown whether the gastrointestinal (GI) tract is affected in other types of NTDs. An absolute requirement for GI motility is the enteric nervous system (ENS) located within the walls of the GI tract. Enteric neurons coalesce into circumferential stripes throughout embryonic, fetal, and early postnatal development, and this gradual organization of the ENS into enteric neuronal stripes correlates with the emergence of neurogenic GI motility. We hypothesized that NTDs are associated with changes in ENS organization that correlate with specific GI motility defects.