Microtubule dynamics as determinants of axon extension and retraction
Funded in: 2014, 2015, 2016
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Problem: After spinal cord injury, connections between neurons are often impaired.
Target: Dynamic changes of the cytoskeleton in axon growth and re-growth after SCI
Goal: Identification of the dynamic changes of the cytoskeleton supporting axon growth as a target for a therapeutic strategy
To receive signals from sensory organs and to transmit signals to effector organs (e.g. muscles), nerve cells are connected to their target cells through long and thin processes called axons. Traumatic injury of the nervous system can sever these axons and thereby disrupt the communication between neurons and their targets while the neurons themselves often survive. It has therefore become a major research focus to promote the re-growth of axons and thereby re-connect surviving neurons to their targets. However, this straightforward concept has met with many obstacles and neurons of the adult central nervous system generally fail to re-grow their severed axons.
The axon is supported by an intra-axonal protein scaffold called the cytoskeleton. In order to support axon maintenance and to promote axon growth, the cytoskeleton needs to be stable and at the same time continuously undergo dynamic rearrangements. Importantly, the delicate balance between stability and dynamic reconfiguration is crucial for successful axon growth.
Therefore, the aim is to investigate what rearrangements of the cytoskeleton are most important for axon growth by analysing neurons as they re-grow their axons in tissue culture.
The team will look at neurons obtained from normal and genetically modified mutant mice lacking a protein (MAP1B) that regulates the cytoskeleton and is essential for efficient axon growth. The neurons also express a marker protein that allows us to track the dynamics of the cytoskeleton under various conditions that either promote or inhibit axon growth.
They expect to determine exactly which dynamic changes of the cytoskeleton support axon growth and which have adverse effects. These results might help to design strategies to support axon re-growth by manipulating the axonal cytoskeleton and on the other hand could reveal which type of dynamic changes has to be avoided.