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

다국어 초록 (Multilingual Abstract)

<P><B>Abstract</B></P> <P>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 <I>in vitro</I>. 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.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Reduced Cdk5 activity inhibits the multipolar-bipolar transition of migrating neurons. </LI> <LI> Ncad expression rescues migration defects caused by the reduction of Cdk5 activity. </LI> <LI> Downregulation of Cdk5 impairs the membrane localization of Ncad. </LI> <LI> Cdk5 and Ncad are present in developing mouse and human brains. </LI> </UL> </P>