Cortical interneurons require p35/Cdk5 for their migration and laminar organization.
Projection neurons and interneurons populate the cerebral cortex in a layer-specific manner. Here, we studied the role of Cyclin-dependent kinase 5 (Cdk5) and its activator p35 in cortical interneuron migration and disposition in the cortex. We found that mice lacking p35 (p35(-/-)) show accumulation of interneurons in the upper part of the cortex. We also observed an inverted distribution of both early- and late-born interneurons, with the former showing a preference for the upper and the latter for the lower aspects of the cortex. We investigated the causes of the altered laminar organization of interneurons in p35(-/-) mice and found a cell-autonomous delay in their tangential migration that may prevent them from reaching correct positions. Incomplete splitting of the preplate in p35(-/-) mice, which causes accumulation of cells in the superficial layer and defects in the "inward" and "outward" components of their radial movement, may also account for the altered final arrangement of interneurons. We, therefore, propose that p35/Cdk5 plays a key role in guiding cortical interneurons to their final positions in the cortex.
Rakić
Sonja
S
Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, UK.
Yanagawa
Yuchio
Y
Obata
Kunihiko
K
Faux
Clare
C
Parnavelas
John G
JG
Nikolić
Margareta
M
D000818:Animals; D002452:Cell Count; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000254:growth & development* / Q000378:metabolism / Q000502:physiology; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D007150:Immunohistochemistry; D007395:Interneurons / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology
D009419:Nerve Tissue Proteins; C089495:neuronal Cdk5 activator (p25-p35); D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse