Neocortical cell migration: GABAergic neurons and cells in layers I and VI move in a cyclin-dependent kinase 5-independent manner

Abstract

The adult mammalian cerebral cortex arises from a complex series of neuronal migrations. The primitive layer known as the preplate is split into an outer marginal zone and an inner subplate by invading cortical plate neurons in an "inside-out" pattern of layering with respect to time of neuronal origin. In cyclin-dependent kinase 5 (Cdk5)-deficient mice (cdk5-/-), the earliest born cortical neurons split the preplate, but later born neurons arrest below the subplate, resulting in an ectopic "outside-in" layer of neurons normally destined for layers II-V. We have pursued this analysis in cdk5-/- ↔ wild-type chimeric mice coupled with experiments in cell culture. In vitro migration assays show no difference in migrational ability between embryonic cdk5-/- and wild-type neurons. In cdk5-/- chimeras, layers I and VI are made up of both mutant and wild-type genotype neurons, whereas layers II-V contain predominantly wild-type cells. In addition, a thin layer of neurons is found below layer VI, made up of cdk5-/- cells; bromodeoxyuridine labeling suggests that these neurons were destined for layers II-V. Scattered cdk5-/- cells are found throughout layers II-V, but these neurons are always found to be GABAergic. The findings suggest that Cdk5 is not required for migration of either the deepest cortical plate neurons or the GABAergic neurons from the ganglionic eminences. The migration of layer II-V pyramidal neurons, however, is intrinsically blocked by Cdk5 deficiency, thus suggesting that different neuronal cell types use distinct mechanisms of migration.