Neurogenetics is the study of the genes that shape neuronal development and function. The genetic approach implies that it is indeed genes, their regulation and their products, that give rise to the complexity of neuronal networks. How can a few thousand genes and their regulatory elements contain the information required to, say, wire a fly's brain to be capable of a feat like computing safe flight in three dimensions? Our lab focusses on understanding the mechanisms that underlie the development, function and maintenance of this neural network.
The Brain Wiring Problem: How Synaptic Specificity is Encoded
Focus: Specification of synaptic partners in the visual map of Drosophila
Specifying synaptic partners and regulating synapse numbers are critical steps during visual map formation that are at least partly activity-dependent in all systems investigated to date. In the Drosophila visual system each photoreceptor forms a precise and constant number of afferent synapses independently of both neuronal activity and synaptic partner accuracy. Our data suggest a cell-autonomous genetic program controlling synapse numbers as part of a developmental program of activity-independent steps that lead to a 'hard-wired' visual map in the fly brain. One major goal of our lab is to understand the molecular and cellular basis of these developmental and genetic programs.
The Maintenance Problem: How Synaptic Contacts and Neurons Stay Alive
Focus: The role of membrane trafficking in synaptic function and maintenance
The same neuron-specific machinery controlling brain wiring may additionally be employed for synaptic function and maintenance. Intracellular vesicle trafficking and endomembrane degradation are known to have important roles for synaptic function and plasticity over long periods of time. Especially the intracellular sorting and degradation machinery are critically required to avoid adult-onset degeneration. We are currently studying the first identified neuron-specific endomembrane degradation mechanism and cargo sorting in several neurodegenerative models in order to understand the sorting of potentially neurotoxic cargo into protective versus toxic compartments. Our genetic approach is complemented with biochemistry, electrophysiology, live imaging and computational visualization techniques.