Molecules - Signaling - Development

Research overview

Our department investigates the common principles and functions of cell-cell communication in the developing and mature nervous system and the molecular mechanisms of neurodegeneration. 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 their environment for the presence of biochemical signals that can be either attractive (adhesive) or repulsive. We are investigating the functions of these signals in a mammalian model organism, the laboratory mouse. Currently, our focus is on the development of the cerebral cortex (Project "Cell-cell communication in the developing brain).

Besides development, we are also interested in understanding how specific neuron populations communicate and contribute to certain types of behavior of adult mice. For these studies, we use genetic methods to gain access to specific microcircuits, we record the activities of well-defined neuron populations in freely behaving mice, we use opto- and pharmacogenetic tools to reveal the functions of these neurons, and we anatomically map the microcircuits. By doing so, we gain insight into how the brain works at the level of individual cell populations. Currently our focus is on amygdala and spinal cord (Project "Circuit dynamics and behavior").

In the context of an ERC-funded project, we are studying the molecular mechanisms of neurodegeneration. Many age-dependent neurodegenerative diseases are characterized by deposition of damaged proteins in the brain. We are using mouse models of human diseases, currently with a focus on Huntington’s disease, to study the effects of these deposits on different types of nerve cells, as well as the mechanisms used by the cells to reduce the accumulation of damaged proteins (Project "Molecular mechanisms of neurodegeneration").

Project Groups

Cell-cell communication in the developing brain

We are investigating the molecular mechanism of cortex folding by studying the function of the FLRT (Fibronectin-Leucin-rich-Transmembrane domain) family of adhesion molecules. Our studies with mutant mice with genetic deletions of FLRT1 and FLRT3 revealed that these mice develop macroscopic cortical sulci with preserved layered organization, an anatomical characteristic of primate brains. We are also studying the ephrin-Eph signaling system, a bidirectional cell-cell communication device with functions in many different physiological processes, including tissue boundary formation and axon guidance.

Circuit dynamics and behavior

We are focusing our analysis on the role of the central amygdala in feeding and reward behavior, and study the specific neural players and circuit mechanisms that positively regulate these behaviors. By using in vivo calcium imaging and optogenetic manipulations, we define the neuronal mechanisms by which the central amygdala promotes consumption of food. Similar approaches are being used to map the circuits in the dorsal horns of the spinal cord that are involved in processing of somatosensory information and sensory-motor integration.

Molecular neurodegeneration

In cooperation with the departments of Ulrich Hartl, Matthias Mann and Wolfgang Baumeister (MPI of Biochemistry), we are characterizing amyloid-like protein aggregates that are a hallmark of several neurodegenerative diseases. To reveal the mechanisms of aggregate toxicity, we are investigating which other cellular proteins interact with the aggregates. By using two-photon calcium imaging in mouse disease models, we aim to uncover the effects of aggregating proteins on neuronal function. We also monitor the status of the cellular defense systems at different stages of disease.