Suster Group
Genetic Dissection of Circuits Controlling Vertebrate Locomotion
Research Interests
Patterned motor tasks such as swimming in fish and walking in humans are the basis of a wide array of behaviors across the animal kingdom. Our group is interested in understanding how such behaviors are generated and controlled by specialized neuronal circuits distributed in the brain and spinal cord. To dissect these complex circuits and their outputs, we focus on genetically identifiable interneuron populations, their neurochemical and electrical properties as well as connections. We use zebrafish (Danio rerio) to selectively visualize and manipulate key interneurons in an intact vertebrate, because its early nervous system is simpler than that of mammals, it is optically transparent, and amenable to large-scale genetic and chemical studies. Major efforts in our group are devoted to developing and applying novel genetic methodology to systematically manipulate the function of locomotor interneurons in zebrafish, including targeted expression of potent neurotoxins and ion channels using gene-trapping and BAC transgenesis. By combining these genetic approaches with patch-clamp electrophysiology and high speed behavioral imaging, we are trying to unravel how interneurons emerge in developing sensorimotor circuits, what role interneurons play in organizing motor behaviors, and ultimately, how specific interneurons can be used to drive complex motor sequences in an intact vertebrate. In the long term, we hope to provide insight into the genetic and evolutionary origin of vertebrate neural circuits, facilitate mechanistic studies of inherited motor disorders, and contribute to the design of novel neurotherapeutic tools.
Current Projects
- How are spinal interneurons uniquely specified? We are examining the regulatory logic underlying the highly restricted expression of molecular determinants (homeodomain transcription factors) in spinal interneurons using transgenic-based reporter assays, cross-species analysis and gene function studies (Suster et al., 2009a).
- Gene-trap based discovery of new interneuron markers and sensorimotor interneurons. Using Gal4 gene trapping (in collaboration with the Kawakami lab) we have discovered several genes that mark previously uncharacterized subpopulations of interneurons, with particular emphasis on commissural interneurons. We are characterizing these lines using a multidisciplinary approach, including fluorescent axonal tracing, dual immunolabelling, gene knockdown, electrophysiology, optogenetics and behavior analysis.
- Targeted expression of new genetically encoded neurotoxins using transposon-mediated BAC transgenesis (Suster et al., 2009c). We have developed the most potent genetically-encoded neurotoxins for targeted silencing of neurotransmission in vertebrates. These are being used in combination with optogenetic cassettes for long-term and chronic silencing and activation of genetically defined interneurons in zebrafish.
Collaborators
- Koichi Kawakami, National Institute of Genetics, Japan
- Wataru Shoji, Tohoku University, Japan
- Philippe Mourrain, Stanford University, USA
- Robert Harvey, London School of Pharmacy, UK
- Uwe Strähle, Karlsruhe Insitute of Technology, Germany
- Gonzalo de Polavieja, Instituto Cajal, Spain
