Molecules - Signaling - Development
Our department is interested in understanding the principles of cell-cell communication in the developing and mature nervous system. Neuronal circuit formation is dependent on the precise navigation of nerve cells (neurons) and their cellular processes (axons and dendrites) to their final destinations. During development neurons explore the surrounding territories for the presence of chemical signals that can be either attractive or repulsive. One group of repulsive guidance signals are the ephrins and their Eph receptors which are produced by many different neurons and their target cells and which play important roles in axon navigation. We are investigating the function of these and other guidance cues in a mammalian model organism, the laboratory mouse (Molecular mechanisms of brain development).
Besides development, we are also interested in understanding how specific neuron populations contribute to certain types of behavior of adult mice. For these studies, we are using genetic methods to alter the circuitry in specific ways and correlate the changes in behavior with the activity of well-defined neuron populations. Combined with the functional dissection of the underlying circuitry and the synaptic connections of the participating neurons, we gain insight into how the brain works at the level of individual cell populations (Circuit analysis and behavior).
Interestingly, the same chemical signals which help neuronal processes to navigate through the embryonic brain also regulate later processes such as synapse formation and learning and memory. By genetically ablating the genes that encode such signals, we can alter the numbers of synapses in certain regions of the brain or reduce the ability of the brain to strengthen frequently excited connections (Synapse development and plasticity).
We are also studying the molecular mechanisms of neurodegeneration and neuroprotection. In recent years, we investigated the functions of endogenous neurotrophic factors and their receptors and explored their potential to prevent neurodegeneration in models of Parkinson’s disease. Many age-dependent neurodegenerative diseases are characterized by deposition of damaged proteins in the brain. Currently we are using mouse models of human diseases to study how these deposits develop, why they are harmful to nerve cells, and which mechanisms are used by the cells to reduce the accumulation of damaged proteins (Molecular mechanisms of neurodegeneration).