Formation and patterning of the avian neuraxis: one dozen hypotheses.

Formation of the neuraxis is dependent on cell-cell interactions and cell movements beginning during stages of gastrulation. Cell movements bring together new combinations of cells, allowing sequential inductive interactions to occur and leading to the specification of the neural plate and to its ultimate mediolateral (subsequently dorsoventral) and rostrocaudal patterning. Formation of the neural plate involves changes in the shape of its constituent cells and the first appearance of neural-specific cell markers. Shortly after the neural plate forms it undergoes 'shaping', in which the pseudostratified columnar epithelium constituting the neural plate thickens apicobasally, narrows transversely and extends longitudinally. Shaping is driven by three principal intrinsic types of cell behaviour: changes in cell shape, position and number. The next stage of neurulation begins while shaping is underway--bending of the neural plate. Bending involves two main processes, furrowing and folding. Furrowing of the neural plate is associated with the formation of the hinge points; these are localized, longitudinal areas where the neuroepithelium is attached to adjacent tissues and where wedging of neuroepithelial cells occurs. Cell wedging in the median hinge point occurs as a result of inductive interactions with the notochord; such wedging drives furrowing, thereby facilitating subsequent folding. Folding of the neural plate requires extrinsic forces generated largely by the surface ectoderm. Types of cell behaviour that could provide such forces include changes in cell shape, position and number. As a result of shaping and bending of the neural plate, the neural folds are brought into apposition in the dorsal midline. Final closure of the neural groove is mediated by cell surface glycoconjugates coating the apical surfaces of the neural folds. Patterning of the neuraxis begins during shaping of the neural plate and continues throughout stages of neurulation and into early postneurula stages. Patterning probably involves inductive interactions with adjacent tissues and the expression of putative positional identity genes such as homeobox-containing genes.