Molecular Neurobiology
Research overview
Our department is interested in understanding the principles of cell-cell communication in the developing nervous system. Neuronal circuit formation is dependent on the precise navigation of nerve cells (neurons) or their progenitor cells from their origin of birth to their final destination. From there, neurons grow cellular processes, axons and dendrites, which explore the surrounding territories for the presence of chemical signals. Neurons use these signals to select the correct brain region and to connect with the correct target cells. Those signals can be soluble or attached to the cell surface. If the neuron finds them attractive, the neuronal process will grow towards the signal. If, however, the neuron is repelled by the signal, the process will change its direction of growth. One group of cell surface-tethered 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 in the central and peripheral nervous system. We investigate the function of these guidance cues and their receptors in a genetically tractable mammalian model organism, the laboratory mouse.
Interestingly, the same chemical signals which regulate the development of the embryonic nervous system, also maintain important functions in the adult brain. The processes of learning and memory induce small morphological changes in the circuits of the brain, known as ‘neuronal plasticity’. Infrequently used connections between neurons disappear, while frequently excited connections are strengthened. Embryonic signals are utilized again for these processes. It is also likely that embryonic signals could be beneficial for the treatment of degenerative changes to stimulate the regeneration of damaged nerves.
We approach these questions at multiple levels: From molecular analyses of individual proteins to cellular investigation of cultured neurons and brain slice preparations, to in vivo analyses of neuronal circuits and behavioral tests of transgenic mice.
Projekt Groups
Interaction of Eph receptors with ephrins presented by an opposing cell leads to repulsion, a process which is only partly understood. The process of contact repulsion is complex and involves the formation of higher order Eph clusters and the bi-directional transcytosis (endocytosis) of the ephrin-Eph complex into the interacting cells. The relationship between clustering, endocytosis and Eph signaling is being investigated in cultured cells.
[more]
It is a long-standing question how millions of neurons manage to connect with their correct target cells and to mature into a functional nervous system. We subject the Ephrin-Eph system to a genetic analysis focusing on several circuits which control locomotion. Individual genes encoding an ephrin or an Eph receptor are genetically ablated in certain regions of the mouse nervous system and resulting changes in circuit development and animal behavior are being investigated.
[more]
Cell-surface proteins with LRR domains play a central role in the establishment of neuronal connections and synapse formation. The family of FLRT proteins (Fibronectin-Leucine-Rich-Transmembrane-proteins) is a newly discovered family of cell-surface proteins with LRR domains. We investigate the various functions of this interesting protein family with a focus on neocortex development.
[more]
A functional circuit is controlled by excitatory and inhibitory synapses. Numbers and efficiencies of synapses can change, a process known as ‘synaptic plasticity’. We find that this process is modulated by Ephrin-Eph signaling complexes and by cell-surface proteins of the subclass of the immunoglobulin superfamily (IgSF). We currently investigate the underlying molecular mechanisms and complement these analyses with genetic studies in mice.
[more]
Endogenous neurotrophic factors regulate the development of the nervous system and maintain the functionality of the aging brain. Declining neurotrophic activity in aging neurons may contribute to pathological neurodegeneration; conversely, the therapeutic increase of neurotrophic activity may slow down the progress of neurodegeneration. We investigate the function of the GDNF (glial cell line-derived neurotrophic factor) receptor in the context of Parkinson disease.
[more]
