Neurotrophin receptors in ephrinA reverse signaling: Investigating axon branching and synaptogenesis. (360G-Wellcome-089611_Z_09_Z)

The retinotectal/collicular projection represents a key model system for studying the formation of topographic projections. Recent data suggest that topographic mapping is controlled through a balance between EphA forward and ephrinA reverse signaling. We are interested in elucidating the mechanisms of ephrinA reverse signaling, in which the neurotrophin receptors TrkB and p75 are involved as candidate ephrinA co-receptors. Our working hypothesis is that both ephrinA/TrkB and ephrinA/p75 inter actions are ligand-inducible. Here the ephrinA/TrkB interaction promotes primarily branching, while the ephrinA/p75 interaction primarily suppresses branching. We would like to demonstrate that on RGC axons the level of ephrinA expression is crucial for the function of TrkB and p75. We then would like to understand on a molecular level the antagonism between ephrinA/TrkB and ephrinA/p75 by analysing their downstream signaling pathways controlling axon branching. We would like to investigate descriptively and functionally the relationship between axon branching and presynapse formation, and their possible regulation by ephrinAs and neurotrophin receptors. Finally we would like to analyse in vivo neurotrophin receptor function in topographic mapping by investigating the retinocollicular projection in TrkB and TrkB/p75 knockout mice.