Martin Schwarz Group
The γ-protocadherin (γ-Pcdh) gene cluster
The mouse γ-Pcdh gene cluster provides an interesting system for studying the formation of stable and specific connections in neuronal networks. Its clustered genomic organization -similar to immunoglobulin and T-cell receptor clusters- and the unusual combinatorial monoallelic mode of expression are compatible with a function in establishing synaptic specificity. To probe the contribution of γ-Pcdh diversity to synaptic wiring in adult mice, we generated a 'floxed' allele of the γ-Pcdh gene cluster by homologous recombination. We utilize transgenic Cre recombinase expressing mouse lines and virus based technologies to generate region specific γ-Pcdh knock-outs.
The effects of these mutations for circuit formation, physiology and behavior are being studied with a focus on the role of γ-Pcdhs in olfactory sensory map formation. The genetic organization of γ-Pcdhs suggests a tantalizing dichotomy, involving polymorphic extracellular domains coupled to a conserved cytoplasmic domain. Thus, to understand γ-Pcdh intracellular signaling in synaptic function of the developing and adult brain we pursue different molecular and biochemical approaches. We are studying proteolytic processing of γ-Pcdhs and the function of the released, conserved intracellular domains in the cell nucleus by gene expression profiling. Furthermore, we utilize mass spectrometric analysis to identify γ-Pcdh interacting proteins.
Virus based methods for manipulation of neuronal circuits
We develop and employ virus-based techniques to label and manipulate specific neuronal subtypes and elucidate transsynaptic connections ‘in vivo’. The viral systems we currently use include: Lenti virus to infect and manipulate neuronal precursor cells to subsequently study their fate; recombinant adeno-associated virus (rAAV) to permit infection and manipulation of large populations of neurons in newborn and adult mice and pseudotyped rabies virus for selective transsynaptic tracing and quantification of distinct neuronal connections in wild-type and genetically modified mice.
Collaborations
Dr. Andreas Frick (Neurocentre Magendie, INSERM U862 University Bordeaux 2), Dr. Valery Grinevich (MPImF), Dr. Andreas Schaefer (MPImF), Dr. Soojin Ryu (MPImF), Prof. Dr. Christian Rosenmund (Neurocure NWFZ Charite Universitaetsmedizin Berlin), Prof. Dr. Karl-Klaus Conzelmann (Gene Center, University of Munich,Max von Pettenkofer-Institute of Virology), Prof. Dr. Kurt Gottmann (Institut für Neuro- und Sinnesphysiologie, Universität Düsseldorf), Prof. Dr. Matthias Klugmann (UNSW, School of Medical Sciences, Sidney), Prof. Dr. Jelena Radulovic (Northwestern University, Chicago).
