Molecular mechanisms of neuronal circuit formation in the developing nervous system.

• Applicant: Dr. Andrea B. Huber Brösamle
• Subject Area: Developmental Neurobiology
• Term: from 2008 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 71600186

During development, axons project to their targets in a step-wise manner in response to attractive and repulsive cues. Their trajectories are broken into short segments, which terminate in specialized regions that form choice points for growing axons. Typically, there is a tight regulation of spatial and temporal patterns of guidance cue expression along axon paths, as well as of the expression of corresponding neuronal receptors. Even though many guidance cues have been identified, we are still far from a comprehensive understanding how complex and accurate neuronal circuitry is established. Major obstacles are presented by the fact that (i) the cues mediating specific growth decisions are still unknown for many choice points and (ii) the fiber projections are often evaluated in isolation without taking neighboring tracts into consideration. However, in vivo, growth cone decisions depend on the interactions of a complex network of neuronal and non-neuronal cells, a multitude of simultaneously detected guidance cues, and the instantaneous integration of all of these inputs. We will address these challenges by a genome-wide screen to identify differentially expressed factors in sensory neurons that are controlling the dorsal-ventral choice in the limb. Using mouse genetic tools to selectively ablate either sensory or motor neurons or remove specific guidance cue receptors in either neuronal subtype we will study the formation of axon trajectories. With this research program we will rigorously test current and novel molecular hypotheses of axon guidance in the whole organism.

• DFG Programme: Research Grants