Elimination of axons occurs as part of the development of the nervous system, after injury or during neurodegenerative disease. The mechanisms that govern this process are poorly understood, and whether the same pathways are operating during development, injury or disease is not known. Through the use of different paradigms of axonal degeneration, we are searching for the molecular pathways that execute axonal breakdown. In parallel, we are investigating the mechanisms that prevent axonal degeneration, enabling the axon to remain intact and functional for the entire life of the organism.
Due to their very long distance from the cell bodies axons depend on mRNA localization and local translation for their function. We aim to uncover basic molecular and cellular principals of this localization machinery - what are the mechanisms that govern mRNA export into the axons? How the axonal local translation is regulated? In parallel we are investigating the importance of axonal mRNA localization to the wiring of the nervous system.
The initial step of the wiring of the nervous system is the guidance of the growing axons from the neurons to their targets. Molecules in the extracellular environment called guidance cues control this directional growth. These cues activate receptors on the responding axons to trigger signaling cascades that steer the axons in the right way. However, the nature of these signaling cascades is largely unknown.
We are combining in vitro axonal guidance assays and state-of-the-art mouse genetics to uncover the guidance receptors signaling domains and their downstream effectors.