appear on both sides of the neural tube simultaneously. Experimental manipulation of the developing somites will not alter the rostral/caudal orientation of the somites, as the cell fates have been determined prior to somitogenesis. Somite formation can be induced by Noggin-secreting cells. The number of somites is species dependent and independent of embryo size (for example, if modified via surgery or genetic engineering). Chicken embryos have 50 somites; mice have 65, while snakes have 500. As cells within the paraxial mesoderm begin to come together, they are termed somitomeres, indicating a lack of complete separation between segments. The outer cells undergo a mesenchymal–epithelial transition to form an epithelium around each somite. The inner cells remain as mesenchyme. Notch signalling The Notch system, as part of the clock and wavefront model, forms the boundaries of the somites. DLL1 and DLL3 are Notch ligands, mutations of which cause various defects. Notch regulates HES1, which sets up the caudal half of the somite. Notch activation turns on LFNG which in turn inhibits the Notch receptor. Notch activation also turns on the HES1 gene which inactivates LFNG, re-enabling the Notch receptor, and thus accounting for the oscillating clock model. MESP2 induces the EPHA4 gene, which causes repulsive interaction that separates somites by causing segmentation. EPHA4 is restricted to the boundaries of somites. EPHB2 is also important for boundaries. Mesenchymal-epithelial transition Fibronectin and N-cadherin are key to the mesenchymal-epithelial transition process in the developing embryo. The process is probably regulated by paraxis and MESP2. In turn, MESP2 is regulated by Notch signaling. Paraxis is regulated by processes involving the cytoskeleton. Specification The Hox genes specify somites as a whole based on their position along the anterior-posterior axis through specifying the pre-somitic mesoderm before somitogenesis occurs. After somites are made, their identity as a whole has already been determined, as is shown by the fact that transplantation of somites from one region to a completely different region results in the formation of structures usually observed in the original region. In contrast, the cells within each somite retain plasticity (the ability to form any kind of structure) until relatively late in somitic development. Derivatives In the developing vertebrate embryo, somites split to form dermatomes, skeletal muscle (myotomes), tendons and cartilage (syndetomes) and bone (sclerotomes). Because the sclerotome differentiates before the dermatome and the myotome, the term dermomyotome refers to the combined dermatome and myotome before they separate