Copper-induced microtubule degeneration and filamentous inclusions in the neuroepithelium of the mouse embryo.

The neuroepithelium of embryos exposed either in vivo or in vitro to copper sulphate was examined by transmission electron microscopy. Exposure to copper sulphate generally resulted in failure of elevation of the neural folds, and consequent development of neural tube defects. These defects appeared to result from the failure of individual cells of the neuroepithelium to change from a low to the high columnar form necessary for normal closure to take place. Ultrastructurally, the neuroepithelial cells showed a considerable reduction in the number of microtubules present, or contained microtubular remnants. Occasionally, deposits of approximately 100A filamentous material were also observed in the middle regions of neuroepithelial cells devoid of microtubules. The overall morphology of individual cells appeared otherwise unchanged. This study supports the concept that microtubules are required for neuroepithelial cellular elongation, an essential step during the process of neurulation. It also suggests that copper, like other microtubule-active agents, may induce the production of characteristic fibrillary deposits that are also observed in a number of neuropathological conditions.