INTRINSIC AND EXTRINSIC FACTORS IN THE MECHANISM OF NEURULATION - EFFECT OF CURVATURE OF THE BODY AXIS ON CLOSURE OF THE POSTERIOR NEUROPORE

Neurulation has been suggested to involve both factors intrinsic and e xtrinsic to the neuroepithelium. In the curly tail (ct) mutant mouse e mbryo, final closure of the posterior neuropore is delayed to varying extents resulting in neural tube defects. Evidence was presented recen tly (Brook et al., 1991, Development 113, 671-678) to suggest that enh anced ventral curvature of the caudal region is responsible for the ne urulation defect, which probably originates from an abnormally reduced rate of cell proliferation affecting the hindgut endoderm and notocho rd, but not the neuroepithelium (Copp et al., 1988, Development 104, 2 85-295). This axial curvature probably generates a mechanical stress o n the posterior neuropore, opposing normal closure. We predicted, ther efore, that the ct/ct posterior 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 neur opore regions, isolated by a cut caudal to the 5th from last somite. I n experimental explants, the neuroepithelium of the posterior neuropor e, together with the contiguous portion of the neural tube, were separ ated mechanically from all adjacent non-neural tissues. The posterior neuropore closed in these explants at a similar rate to isolated poste rior neuropore regions of non-mutant embryos. By contrast, control ct/ ct explants, in which the caudal region was isolated but the neuroepit helium was left attached to adjacent tissues, showed delayed neurulati on. 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-deg rees per mm axial length), of either concave or convex nature, resulte d in delay of posterior neuropore closure in the chick embryo. Both in cidence and extent of closure delay correlated with the degree of curv ature that was imposed. We propose that during normal embryogenesis th e rate of neurulation is related to the angle of axial curvature, such that experimental alterations in curvature will have differing effect s (either enhancement or delay of closure) depending on the angle of c urvature at which neurulation normally occurs in a given species, or a t a given level of the body axis.