Molecular mechanisms driving the formation of the neuronal microtubule cytoskeleton

Microtubule polymers are part of a vast network inside cells called the cytoskeleton. This network, although highly dynamic, can be specifically arranged to perform different cellular functions. During cell division, the cytoskeleton forms the mitotic spindle, a compact force-generating structure that separates the duplicated DNA. In contrast, during brain development the organisation is quite different, with extensive parallel structures forming inside the neurons. How the cytoskeleton can undergo such dramatic shape changes to perform specialised tasks is poorly understood. Many microtubule-associated proteins (MAPs), including stabilisers and destabilisers, operate to tune the cytoskeleton. I found that some MAPs of the mitotic spindle are also active during neurogenesis. Also, mutations in them are linked to human neurodevelopmental disorders.

I will combine genetic tools with light microscopy to understand how these proteins function and how their overall activity contributes to shaping the neuronal cytoskeleton in the model organism C. elegans and human cells.

This research will provide an insight into MAPs which could inform research into neurodevelopmental disorders.