Birth defects (congenital anomalies) are the leading cause of death in babies under 1 year of age. Neural tube defects (NTD), with a birth incidence of approximately 1/1000 in American Caucasians, are the second most common type of birth defect after congenital heart defects. In humans, the most common NTD are anencephaly and myelomeningocele. Anencephaly results from a failed closure of the rostral end of the neural tube and is characterized by a total or partial absence of the cranial vault and cerebral hemisphere. Myelomeningocele is a defective closure of the neural tube in the vertebral column. Depending on the size and the location of the defect, the patient can suffer either no physical handicap or lifelong disabilities . These common birth defects vary in frequency depending on the geographical localization. They occur at frequencies ranging from 0.9 in Canada to 7.7 in the United Arab Emirates and 0.7 in central France to 11.7 in South America per 10,000 births, for anencephaly and spina bifida respectively . The mortality rate for children with spina bifida is increased over the general population risk in the first year of life. The cost of providing for medical care for a child with myelomeningocele has been estimated to be over $70,000 (adjusted to 2001 dollars) annually for the first 20 years of life, including costs associated with an average of 5 surgeries per year  in the first five years of life (20 year lifetime cost is $1.4 million/case). The phenotypes of the open NTDs include myelomeningocele (spina bifida cystica, open spina bifida) and anencephaly. Anencephaly, an incomplete formation of the brain and skull, is uniformly lethal. The most common form of NTD, myelomeningocele, is an open lesion in the caudal spine and contains dysplastic spinal cord, often resulting in a lack of neural function below the level of the defect. Affected patients usually have reduced ability to walk, or need the use of a wheelchair, have little or no bowel and/or bladder control, and require frequent surgical interventions to minimize the effects of hydrocephalus. The most common presentations, spina bifida and anencephaly, can occur within the same family, raising the question as to whether these phenotypes are related and due to a common underlying gene [29,29,31,33,38,65,65,77,77]. Defining the phenotype in affected patients is paramount to the evaluation of human neural tube defects. Phenotypic parameters include: location and level of the defect, whether the defect crosses CNS segmental boundaries, and cataloguing the variety of anomalies in a patient or family. Open defects such as anencephaly, cranioraschisis, myelomeningocele, and myeloschisis are defined based upon the location and level and are descriptive in nature. Associated anomalies, Chiari II, hydrocephalus, syringomyelia, polymicrogyria, cortical heterotopias, agenesis of the corpus callosum further add to and can confuse the phenotypic definitions. NTDs in humans result from the combined effects of genetic and environmental influences, and as such are a classic example of a multifactorial disorder. Identifying the genetic factors is critical for characterizing the interactions between genes and the environment, and understanding these interactions will provide the basis for designing novel preventive strategies and for offering accurate reproductive risks to couples. The genetic factors will likely involve aberrant variations in genes key for the normal closure of the neural tube. Neural tube closure is a complex, early developmental process, informed not only by nascent studies in human embryos, but by the plethora of investigations in a variety of experimental systems including but not restricted to mouse, zebrafish, and chick.