future induction and formation of the neural tube. Closure of the neural tube is completed when the neural folds are brought together, adhering to each other. While the cells that remain as the neural tube form the brain and spinal cord, the other cells that were part of the neural plate migrate away from the tube as neural crest cells. After an epithelial–mesenchymal transition, these cells form the autonomic nervous system and certain cells of the peripheral nervous system. Cell signaling and essential proteins Critical to the proper folding and function of the neural plate is N-cadherin, a type of cadherin protein associated with the nervous system. N-cadherin is critical to holding neural plate cells together. Additionally, cells destined to become neural plate cells express nerve cell adhesion molecule (NCAM) to further neural plate cohesion. Another cadherin, E-cadherin, is expressed by ectodermal cells in the process of neural plate development. Bone morphogenetic protein 4, or BMP4, is a transforming growth factor that causes the cells of the ectoderm to differentiate into skin cells. Without BMP4 the ectoderm cells would develop into neural cells. Axial mesoderm cells under the ectoderm secrete inhibitory signals called chordin, noggin and follistatin. These inhibitory signals prevent the action of BMP4, which would normally make the cells ectoderm; as a result, the overlying cells take their normal course and develop into neural cells. The cells in the ectoderm that circumscribe these neural cells do not receive the BMP4 inhibitor signals and as a result BMP4 induces these cells to develop into skin cells. Neural plate border specifiers are induced as a set of transcription factors. Distalless-5, PAX3 and PAX7 prevent the border region from becoming either neural plate or epidermis. These induce a second set of transcription factors called neural crest specifiers, which cause cells to become neural crest cells. In a newly formed neural plate, PAX3 mRNA, MSX1 mRNA, and MSX1/MSX2 proteins are expressed mediolaterally. When the neural plate begins to fold, rostral areas of the neural plate do not express Pax3 and MSX proteins. Areas caudal to neural tube closure have PAX3 and MSX expression restricted to lateral regions of the neural folds. These fluctuations in mRNA and protein expression allude to how they play a role in differentiation of neural plate cells. Low pSMAD 1, 5, 8 levels allow a greater mobility at the median hinge point than in lateral neural plate cells.