Neural Crest development
The neural crest is a transient structure that extends along the rostro-caudal axis of developing vertebrate embryos. It comes into existence during the final stages of neurulation. The primary embryonic induction initiates and controls neurulation. The notochord and adjacent mesoderm interact with the overlying dorsal ectoderm. This interaction induces the ectoderm to thicken, flatten and rise above the surrounding ectoderm, forming the neural plate. This thickening is caused by cell shape changes. The edges of the plate are drawn up by further cell shape changes into neural folds.
The embryo becomes separated into two halves by the appearance of the neural groove running along the centre of the neural plate1. The neural folds come together along the midline of the neural plate and fuse. The movement of the neural folds is generated by changes in the shape of the cells within the folds and the neural plate. The fusion of the neural folds “pinches off” the neural tube as a hollow cylinder of ectoderm, lying beneath the remaining surface ectoderm. The region of the embryo that lies between the newly formed neural tube and the surface ectoderm is composed of the neural crest cells.
Prior to neurulation, gastrulation creates the three germ layers and organises them within the embryo. Following gastrulation the surface of the embryo consists of ectoderm. Beneath the ectoderm lies the mesodermal layer and still further inside the embryo the endoderm is found. The neural crest is found only in vertebrate embryos and is often cited as a defining characteristic of vertebrate organisms. The neural crest contains a migratory population of cells that give rise to most of the peripheral nervous system, facial skeleton and numerous other derivatives throughout the embryo.
2 The tissues and organs of developing embryos are ordered by cell-to-cell communication. These interactions are mediated by a moderately small number of signalling molecules. These signals are continually used at different stages of development and in different tissues of the embryo. Experiments have shown evidence that induction of the neural crest can be initiated by interactions between the ectoderm and neural plate. The established view is that a signal originates from the ectoderm and is received in the neuroepithelium. The addition of growth factors to nai??
ve neural plate tissue has shown possible molecules with the capability to initiate neural crest formation. Such molecules include, transforming growth factors, (TGF-? ), bone morphogenetic proteins; BMP-4 and BMP-7, and activin. These molecules are thought to be the ectodermal-inducing signal. 3 (Liem et al. 1993) At the border region between the ectoderm and neural plate, induction is continuous and BMP’s are expressed ephemerally in the caudal-most ectoderm. Nonetheless, most ubiquitous BMP expression at this point is in the neural folds and dorsal neural tube, with faint expression in the ectoderm.
Lower expression of BMP in inducing tissue than in the responding tissue shrouds the analysis of its function. As a result, the fundamental nature of the “ectodermal inducer” is ambiguous. 4 (Basch et al. 2000) The Wnt family of genes encode secreted glycoproteins that function as signals in cell-to-cell communication during animal embryonic development. The segment polarity gene wingless in Drosophila and the proto-oncogene int-1 (Wingless + iNT-1 = WNT) are the best-known members of this class, but Wnt genes have also been found in animals ranging from the nematode worm C.
elegans to vertebrates such as the amphibian and humans. Abnormally expressed Wnt’s are suspected to be involved in certain types of tumours such as breast and colon cancer. 5 Much of what is known about the functional role of Wnt signalling in early vertebrate development and neural crest induction comes from experiments with Xenopus laevis. Maternally encoded components of the canonical Wnt signalling pathway function to establish the endogenous dorsal axis. Wnt signalling in most tissues is thought to be mediated by the canonical Wnt signal transduction pathway.
The extracellular Wnt ligands bind to the transmembrane receptor Frizzled (Fz) which are secreted glycoproteins that play a role in both embryonic development and tumorigenesis. This binding activates the cytoplasmic phosphoprotein Dishevelled (dsh). Activated Dishevelled (dsh) inhibits GSK3i?? -mediated degradation of i?? -catenin. i?? -catenin protein therefore accumulates and in association with transcription factors (Tcf-3) regulates gene transcription in the cell nucleus. 6 The Wnt signalling system is one of only a limited number of signalling systems used during embryonic development to pattern the body plan.