Role of Citron K in the development of cerebral cortex

Citron-K (CIT-K) is a target molecule for activated Rho which is expressed at high levels in the proliferating areas of the CNS from E10.5 to E16. CIT-K -/- mice display severe defects in neurogenesis, due to altered cytokinesis and aptoptosis: these cellular alterations result in severe microencephaly and in death of the animal due to fatal seizures between the 2nd and the 3rd week of age. We have analysed the development of somatosensory cortex in the CIT-K -/- mice, showing i) a decrease in the barrelfield area and in the size of single whisker-related barrels, ii) a decrease in the cortical thickness, especially in supragranular layers, iii) a decrease in the density of myelinated fibers. We also report cellular changes in cortical neurons: i) both pyramidal neurons and interneurons show altered dendritic development and frequent polyploidy, and ii) the distribution of interneurons is affected by CIT-K deletion. CIT-K -/- mice are a useful tool to study the role of this molecule in the cellular development of cerebral cortex in vivo, and the development and plasticity of cortical areas and connections in a microencephalic animal. Moreover, they represent an interesting model of neonatal epilepsy, in which to study the role of changes in cellular morphology and interneuron distribution in the genesis of epileptic seizures.