Intrinsic and extrinsic factors in the mechanism of neurulation: effect of curvature of the body axis on closure of the posterior neuropore.

ABSTRACT

Neurulation has been suggested to involve both factors intrinsic and extrinsic to the neuroepithelium. In the curly tail (ct) mutant mouse embryo, final closure of the posterior neuropore is delayed to varying extents resulting in neural tube defects. Evidence was presented recently (Brook et al., 1991 Development 113, 671-678) to suggest that enhanced ventral curvature of the caudal region is responsible for the neurulation defect, which probably originates from an abnormally reduced rate of cell proliferation affecting the hindgut endoderm and notochord, but not the neuroepithelium (Copp et al., 1988, Development 104, 285-295). This axial curvature probably generates a mechanical stress on the posterior neuropore, opposing normal closure. We predicted, therefore, that the ct/ct posterior neuropore should be capable of normal closure if the neuropore should be capable of normal closure if the neuroepithelium is isolated from its adjacent tissues. This prediction was tested by in vitro culture of ct/ct posterior neuropore regions, isolated by a cut caudal to the 5th from last somite. In experimental explants, the neuroepithelium of the posterior neuropore, together with the contiguous portion of the neural tube, were separated mechanically from all adjacent non-neural tissues. The posterior neuropore closed in these explants at a similar rate to isolated posterior neuropore regions of non-mutant embryos. By contrast, control ct/ct explants, in which the caudal region was isolated but the neuroepithelium was left attached to adjacent tissues, showed delayed neurulation. To examine further the idea that axial curvature may be a general mechanism regulating neurulation, we cultured chick embryos on curved substrata in vitro. Slight curvature of the body axis (maximally 1 degree per mm axial length), of either concave or convex nature, resulted in delay of posterior neuropore closure in the chick embryo. Both incidence and extent of closure delay correlated with the degree of curvature that was imposed. We propose that during normal embryogenesis the rate of neurulation is related to the angle of axial curvature, such that experimental alterations in curvature will have differing effects (either enhancement or delay of closure) depending on the angle of curvature at which neurulation normally occurs in a given species, or at a given level of the body axis.