Dendritic and synaptic remodeling and the role of microRNAs during peripheral motor nerve de- and regeneration

• Applicant: Dr. Juliane Bremer
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2012 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 231789167

Damage to peripheral nerves is caused by a wide variety of insults and although peripheral nerves have retained the capacity for regeneration, even with the best available therapies, functional recovery is often incomplete. Thus there is an urgent need to identify novel enhancers of nerve regeneration. Previous studies have shown that motoneuron dendrites and synapses diminish following axonal injury, and upon target reinnervation increase again, yet the significance of this process for nerve regeneration has not been established. Similarly, gene expression in motoneurons is shifted from a signal-transmitting to a regeneration-promoting state, and while it is clear that small regulatory microRNAs are important for sensory axon regeneration, their function in motoneurons following axon injury is unknown. Here, I will utilize a recently developed zebrafish system to study motoneuron de- and regeneration in live intact animals. Specifically, I will take advantage of the optical transparency, the ease of genetic manipulations and live cell imaging of zebrafish to first document motoneuronal dendrite and synapse dynamics as well as excitability during axonal degeneration and regeneration in real time. Furthermore, I will identify a complement of motoneuron-specific regeneration-associated microRNAs by sequencing, and test their in vivo functions during motor axon regeneration, including their roles in dendritic and synaptic remodeling. Thus, the proposed experiments will provide the first account of injury-induced dendritic and synaptic remodeling in vivo, and will also identify key regeneration-associated microRNAs required for this process.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Michael Granato