Guidance of Cortical Interneuron Migration: Model Systems for interneuropathies
(Kiara Aiello, Sandra Clemens, Annika Döding, Céline Heng, Alina Moyé, Ann-Kathrin Pilz, Judith Rudolph and Jürgen Bolz)

Cortical interneurons control the flow of information and synchronization in neuronal circuits and they accomplish their specific functions through a remarkable diversity of subtypes. Disruption in the number and/or composition of interneuron subtypes can lead to neurological or psychiatric disorders. During development, most cortical interneurons are generated in the basal telencephalon and they then migrate tangentially over long distances towards and into the cortex. In this research project we study the roles of the Eph/ephrin system – a large family of brain wiring genes - in regulating interneuron migration. For this we examine the spatial and temporal expression pattern of the complete Eph/ephrin gene family in the developing telencephalon. In combination with sensitive in vitro bioassays for the functional characterization of selected members of the Eph/ephrin system on interneuron migration, we can make specific predictions about their putative functions during forebrain development. To test these hypotheses directly in vivo, we use in utero mediated gene transfer and transgenenic technology to generate mice where members of the Eph/ephrin gene family are down-regulated selectively in cortical interneurons. The ultimate goal of this line of research is to produce model animals with defined alterations in the composition of cortical interneurons that mimic some aspects of the pathophysiology observed in some diseases of the brain, collectively described as interneuropathies.