Ultrastructural analysis of chromosome translocation-induced neural tube defects

Neural tube closure defects occurred in 33% of the embryos obtained from matings of male mice heterozygous for a reciprocal chromosome translocation (T(2;4)1Sn) with normal female CFLP mice. Light and electron microscopic observations of neuroepithelium and mesenchyme in affected embryos indicated two distinct types of anomalies occurred. The first consisted of neuroepithelial hypertrophy and neural tube closure defects. These defects most frequently affected the midbrain and hindbrain, but occasional defects of the lumbosacral neural tube were also observed. Unlike the highly organized, pseudostratified neuroepithelium in control embryos, neuroepithelial cells became stratified and formed cell islands with secondary lumina within the wall of the neural tube. The second condition was associated with a reduction in neuroepithelial thickness, considerable neuroepithelial and neural crest cell death, basal lamina alterations and premature invasion of the neuroepithelium by subjacent endothelial cells. In both cases, the cephalic mesenchyme cells, rather than their normal stellate appearance, were markedly elongated in shape and reduced in area. The number of cell-cell contacts between mesenchymal cells was also reduced significantly. These results are discussed in light of recent theories regarding the role of mesenchyme and extracellular matrix in neurulation.