Cdk5 regulates N-cadherin-dependent neuronal migration during cortical development

Abstract

Cyclin-dependent kinase 5 (Cdk5) controls neuronal migration in the developing cortex when multipolar newborn neurons transform to become bipolar. However, by which mechanisms Cdk5 controls cell adhesion in migrating neurons are not fully understood. In this study, we examined the functional interaction between Cdk5 and N-cadherin (Ncad) in newborn neurons when they undergo the multipolar to bipolar transition in the intermediate zone (IZ). Detailed expression analysis revealed that both Cdk5 and Ncad were present in GFP-electroporated migrating neurons in the IZ. Misexpression of dominant negative Cdk5 into the embryonic brains stalled neuronal locomotion in the lower IZ in which arrested cells were round or multipolar. When Ncad was co-introduced with Cdk5DN, however, cells continue to migrate into the cortical plate (CP) and migrating neurons acquired typical bipolar morphology with a pia-directed leading process. Similarly, downregulation of CDK5 resulted in lesser aggregation ability, reversed by the expression of Ncad in vitro. Down-regulation of activity or protein level of CDK5 did not alter the total amount of NCAD proteins but lowered its surface expression in cells. Lastly, expression of CDK5 and NCAD overlapped in the IZ of the human fetal cortex, indicating that the role of Cdk5 and Ncad in neuronal migration is evolutionarily conserved.

Keywords: Cdk5; N-cadherin; Neuronal locomotion.