Analysis of neurulation in a mouse model for neural dysraphism.

Elongation of the neuraxis was analyzed quantitatively with respect to the subpopulation of longitudinally oriented mitoses in the neuroepithelium in homozygous embryos of the loop-tail (Lp) mutant mouse, which is characterized by failure of fusion of the neural folds from the midbrain to the tail, as well as a shortening of the neuraxis. Correlations were made with mitotic cell orientation in the underlying gut and notochord, which are likewise shortened. In the abnormal dysraphic embryos at the 7- to 11-somite stage, the percentage of longitudinally oriented mitotic spindles in the neuroepithelium was significantly less than in normal embryos. In contrast, significant differences were not obtained with respect to the orientation of mitotic spindles in the gut or notochord. At the 15- to 20-somite stage, significant differences in mitotic orientation in the neuroepithelium, gut, or notochord did not occur between dysraphic and normal embryos. The results suggest that during elevation and fusion of the neural folds, a decrease in the percentage of longitudinally arranged spindles in the neuroepithelium of Lp/Lp embryos may contribute to the disturbance in neuraxial elongation and possibly closure failure, but that the shortened gut and notochord that also characterize this mutant may not result from defective orientation of mitotic spindles.