Glial-neuron crosstalk in the regulation of neurofilament dynamics

ended

Accurate communication between the central nervous system and the periphery requires rapid and efficient transmission of action potentials along the axon. Glial cells and neurons cooperate to regulate axonal conduction, and normal physiology of the nervous system is strongly dependent on the crosstalk between the two systems. Neurofilaments (NFs), the most abundant components of the neuronal cytoskeleton are a key target of the crosstalk that regulates electrical conductance. Nevertheless, the mechanisms by which the glial-neuron crosstalk regulates NF dynamics are currently not well understood. Yet this knowledge is of great importance, as disturbances in this system underlie disease mechanisms in various neurodegenerative diseases. In the GliaNFish project, top-notch techniques will be combined to capture for the very first time real-time dynamics of NF transport and NF-protein interactions in a living organism (zebrafish larvae), to understand the role of glia-neuron crosstalk in nervous system physiology. The project encompasses three objectives which aim to investigate: 1) NF organization and dynamics in vivo; 2) the impact of (de)myelination on NF organization and dynamics; and 3) the molecular players involved in the outside-in signalling cascade that regulate NF dynamics. The outcomes of the project will advance our understanding of NF dynamics and signalling in vivo, and on how myelinating glia and neurons synergize to enable signal conduction in the nervous system. This knowledge may permit in the future to explore how disturbances in this system lead to disease and will pave the way for novel therapeutic strategies towards NF dynamics. Overall, this project is extremely timely and relevant, as the social and economic burden of neurodegenerative diseases is expected to rise significantly in the upcoming years.