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. Bromodeoxyuridine labeling reveals that the normal inside-out neurogenic gradient is inverted in the mutants; earlier born neurons are most often found superficial to those born later. Despite this, the early preplate layer separates correctly and neurons with a normal, pyramidal morphology can be found between true marginal zone and subplate. Consistent with their identity as layer VI corticothalamic neurons, they can be labeled by DiI injections into thalamus. The DiI injections also reveal that the trajectories of the cdk5(-/-) thalamocortical axons are oblique and cut across the entire cortical plate, instead of being oriented tangentially in the subcortical white matter. We propose a model in which the cdk5(-/-) defect blocks cortical development at a heretofore undescribed intermediate stage, after the splitting of the preplate, but before the migration of the full complement of cortical neurons.
Department of Neuroscience, Case Western Reserve Medical School, Cleveland, Ohio 44106, USA.
E C
EC
Gilmore
T
T
Ohshima
A M
AM
Goffinet
A B
AB
Kulkarni
K
K
Herrup
D000818:Animals; D001973:Bromodeoxyuridine; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000196:embryology* / Q000473:pathology; D002809:Chondroitin Sulfates / Q000378:metabolism; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases; D004622:Embryo, Mammalian / Q000033:anatomy & histology; D005314:Embryonic and Fetal Development / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D051379:Mice / Q000196:embryology / Q000235:genetics; D009154:Mutation / Q000502:physiology*; D009419:Nerve Tissue Proteins; D009434:Neural Pathways / Q000196:embryology; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000091042:Reelin Protein; D012697:Serine Endopeptidases; D013788:Thalamus / Q000196:embryology
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D002809:Chondroitin Sulfates; D051360:Cyclin-Dependent Kinase 5; D017346:Protein Serine-Threonine Kinases; C495906:Cdk5 protein, mouse; D018844:Cyclin-Dependent Kinases; D012697:Serine Endopeptidases; D001973:Bromodeoxyuridine