CYCLIN-DEPENDENT KINASE 5-DEFICIENT MICE DEMONSTRATE NOVEL DEVELOPMENTAL ARREST IN CEREBRAL-CORTEX

The cerebral cortex of mice with a targeted disruption in the gene for cyclin-dependent kinase 5 (cdk5) is abnormal in its structure. Bromod eoxyuridine labeling reveals that the normal inside-out neurogenic gra dient is inverted in the mutants; earlier born neurons are most often found superficial to those born later. Despite this, the early preplat e layer separates correctly and neurons with a normal, pyramidal morph ology can be found between true marginal zone and subplate. Consistent with their identity as layer VI corticothalamic neurons, they can be labeled by Dil injections into thalamus. The Dil injections also revea l that the trajectories of the cdk5(-/-) thalamocortical axons are obl ique and cut across the entire cortical plate, instead of being orient ed tangentially in the subcortical white matter. We propose a model in which the cdk5(-/-) defect blocks cortical development at a heretofor e undescribed intermediate stage, after the splitting of the preplate, but before the migration of the full complement of cortical neurons.