Pathogenesis of neural dysraphism in the mouse mutant vacuolated lens (vl).

The pathogenesis and expression of caudal neural dysraphism were studied by means of tritiated thymidine autoradiography in the mouse mutant vacuolated lens (vl) at 11-13 days of gestation. In homozygous litters, all of the embryos microscopically exhibited spinal cord defects, even though dysraphism could be detected grossly only in the most severely affected ones. The defects ranged from extreme eversion of widely open neural folds to a dorsally expanded neurocoel with an attenuated or distorted roof plate. Incorporation of tritiated thymidine occurred in cells in the defective roof plates, in severely distorted areas of the neural tube where cellular disaggregation occurred, and in isolated areas within the developing intermediate layer, as well as in normal sites of cellular proliferation. The frequently observed central mass of distorted but proliferating neural tissue associated with bilateral attenuations of the roof plate suggests a failure of, or defect in, the normal process of apposition and fusion of the neural folds, rather than a failure in opposition. The range in severity and the gross and microscopic manifestations of neuropathological lesions in the homozygous vl embryos indicate that this heretofore unexplored mutant has considerable potential as an experimental model for analyzing the origins and mechanisms of human neural dysraphism.