Send to

Choose Destination
Annu Rev Genet. 2014;48:583-611. doi: 10.1146/annurev-genet-120213-092208. Epub 2014 Oct 6.

Genetic, epigenetic, and environmental contributions to neural tube closure.

Author information

Department of Pediatrics, University of Colorado Anschutz Medical Campus, Children's Hospital Colorado, Aurora, Colorado 80045; email:


The formation of the embryonic brain and spinal cord begins as the neural plate bends to form the neural folds, which meet and adhere to close the neural tube. The neural ectoderm and surrounding tissues also coordinate proliferation, differentiation, and patterning. This highly orchestrated process is susceptible to disruption, leading to neural tube defects (NTDs), a common birth defect. Here, we highlight genetic and epigenetic contributions to neural tube closure. We describe an online database we created as a resource for researchers, geneticists, and clinicians. Neural tube closure is sensitive to environmental influences, and we discuss disruptive causes, preventative measures, and possible mechanisms. New technologies will move beyond candidate genes in small cohort studies toward unbiased discoveries in sporadic NTD cases. This will uncover the genetic complexity of NTDs and critical gene-gene interactions. Animal models can reveal the causative nature of genetic variants, the genetic interrelationships, and the mechanisms underlying environmental influences.


embryonic brain; embryonic spinal cord; gene-environment interactions; neural tube defects, epigenetics

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center