Current research

Layering and wiring of neurons in the cerebral cortex

During development of the cerebral cortex, postmitotic neurons migrate from the ventricular zone towards the marginal zone and form the layered structure of the cerebral cortex. Correct positioning and development of cortical neurons is controlled by Reelin, a protein that is expressed and secreted by Cajal Retzius (CR) cells, early generated neurons which are located in the marginal zone of the developing cortex (Förster et al., 2006). Reelin effects on cytoskeletal elements of migrating neurons and on synaptic transmission of adult neurons are mediated by the apolipoprotein E receptor 2 (ApoER2) and the very low density lipoprotein receptor (vldlr), both of which are receptors of the lipoprotein receptor family. Deficiency for Reelin or its receptors leads to severe neuronal migration defects. Reelin deficiency in the developing human cerebral cortex causes lissencephaly, a malformation that is associated with severe mental retardation. It is poorly understood how Reelin modulates neuronal function in the adult brain, where this protein is expressed by interneurons. The objective of our present research is to characterize Reelin dependent functions of neurons in both the developing and the adult brain. We are currently using a conditional Reelin-deficient mouse mutant as a model to study the effects of induced Reelin deficiency at specific time points. In our experiments, we combine histology, molecular biological techniques and cell biological techniques with confocal microscopy as well as live cell imaging of cultured neurons and organotypic slice cultures.