Aberrant lamination in the cerebral cortex of mouse embryos lacking DNA topoisomerase IIbeta.

We have examined corticogenesis in mouse embryos lacking DNA topoisomerase IIbeta (IIbeta) in the brain or in all tissues. The absence of IIbeta, a type II DNA topoisomerase normally expressed in postmitotic cells in the developing cortex, severely affects cerebral stratification: no subplate is discernible, and neurons born at later stages of corticogenesis fail to migrate to the superficial layers. This abnormal pattern of neuron positioning in the cerebral cortex is reminiscent of that observed in mouse mutants defective in the reelin-signaling pathway. Significantly, the level of reelin in the neocortex is much reduced when IIbeta is absent. These results implicate a role of IIbeta in brain development. The enzyme may be required in implementing particular genetic programs in postmitotic cells, such as reelin expression in Cajal-Retzius cells, perhaps through its action on nucleoprotein structure of particular chromosomal regions.