of the cell to change. This process is known as apical constriction. The result is a flattening of the differentiating neural plate which is particularly obvious in salamanders when the previously round gastrula becomes a rounded ball with a flat top. See Neural plate Folding The process of the flat neural plate folding into the cylindrical neural tube is termed primary neurulation. As a result of the cellular shape changes, the neural plate forms the medial hinge point (MHP). The expanding epidermis puts pressure on the MHP and causes the neural plate to fold resulting in neural folds and the creation of the neural groove. The neural folds form dorsolateral hinge points (DLHP) and pressure on this hinge cause the neural folds to meet and fuse at the midline. The fusion requires the regulation of cell adhesion molecules. The neural plate switches from E-cadherin expression to N-cadherin and N-CAM expression to recognize each other as the same tissue and close the tube. This change in expression stops the binding of the neural tube to the epidermis. The notochord plays an integral role in the development of the neural tube. Prior to neurulation, during the migration of epiblastic endoderm cells towards the hypoblastic endoderm, the notochordal process opens into an arch termed the notochordal plate and attaches overlying neuroepithelium of the neural plate. The notochordal plate then serves as an anchor for the neural plate and pushes the two edges of the plate upwards while keeping the middle section anchored. Some of the notochodral cells become incorporated into the center section neural plate to later form the floor plate of the neural tube. The notochord plate separates and forms the solid notochord. The folding of the neural tube to form an actual tube does not occur all at once. Instead, it begins approximately at the level of the fourth somite at Carnegie stage 9 (around Embryonic day 20 in humans). The lateral edges of the neural plate touch in the midline and join together. This continues both cranially (toward the head) and caudally (toward the tail). The openings that are formed at the cranial and caudal regions are termed the cranial and caudal neuropores. In human embryos, the cranial neuropore closes approximately on day 24 and the caudal neuropore on day 28. Failure of the cranial (superior) and caudal (inferior) neuropore closure results in conditions called anencephaly and spina bifida, respectively.