Molecular and cellular mechanisms regulating axonal branching

A central goal in developmental neuroscience is to elucidate the cellular and molecular mechanisms behind the formation, refinement, and maintenance of neural networks. Both during embryonic development and in diseases, failure to form adequate neural connections may result in severe disabilities. A critical event in the setting up of neuronal circuits is axonal branching. Indeed, control of axonal branching formation and retraction allows neurons to make connection with several targets, therefore playing an important in the formation of neuronal circuits. However, the mechanisms leading to axonal branching in vivo are poorly understood. This is in part due to a lack of tools with which to observe branching in real time and in vivo.
We have recently reported that the PLCγ -Ca2+ pathway downstream of BDNF (Brain Derived Neurotrophin Factor) signalling plays a crucial role in the regulation of axonal branching in otoneurons (Panagiotaki et al. 2010). Furthermore, we have established a system allowing us to express tran sgenes specifically in Xenopus motoneurons. We will use this technology to address the role of the cytoskeleton and different signalling pathways in axonal branching in vivo. Finally, we will use new technology to generate a knock-out of a Ca2+ regulator specifically expressed in motoneurons (Spry3) and analyse the effects at the molecular, cellular and functional levels.
Our combined expertise places us in a unique position to uncover the in vivo mechanisms regulating axonal branching in motoneurons, an essential process for the correct wiring of the nervous system.