<P> Subsequent work on inducers by scientists over the 20th Century demonstrated that not only could the dorsal lip of the blastopore act as an inducer but so could a huge number of other seemingly unrelated items . This began when boiled ectoderm was found to still be able induce by Johannes Holtfreter . Items as diverse as low pH, cyclic AMP, even floor dust could act as inducers leading to considerable consternation . Even tissue which could not induce when living could induce when boiled . Other items such as lard, wax, banana peels and coagulated frog's blood did not induce . The hunt for a chemically based inducer molecule was taken up by developmental molecular biologists and a vast literature of items shown to have inducer abilities continued to grow . More recently the inducer molecule has been attributed to genes and in 1995 there was a call for all the genes involved in primary neural induction and all their interactions to be catalogued in an effort to determine "the molecular nature of Spemann's organizer". Several other proteins and growth factors have also been invoked as inducers including soluble growth factors such as bone morphogenetic protein, and a requirement for "inhibitory signals" such as noggin and follistatin . </P> <P> Even before the term induction was popularized several authors, beginning with Hans Driesch in 1894, suggested that primary neural induction might be mechanical in nature . A mechanochemical based model for primary neural induction was proposed in 1985 by Brodland & Gordon . An actual physical wave of contraction has been shown to originate from the precise location of the Spemann organizer which then traverses the presumptive neural epithelium and a full working model of how primary neural inductions was proposed in 2006 . There has long been a general reluctance in the field to consider the possibility that primary neural induction might be initiated by mechanical effects . A full explanation for primary neural induction remains to be found . </P> <P> As neurulation proceeds after induction the cells of the neural plate become high - columnar and can be identified through microscopy as different from the surrounding presumptive epithelial ectoderm (epiblastic endoderm in amniotes). The cells move laterally and away from the central axis and change into a truncated pyramid shape . This pyramid shape is achieved through tubulin and actin in the apical portion of the cell which constricts as they move . The variation in cell shapes is partially determined by the location of the nucleus within the cell, causing bulging in areas of the cells forcing the height and shape 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 </P> <P> 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 causes 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 . Neural plate folding is a complicated step . </P>

Primary neurulation begins in response to signals released by cells in the