Spinal muscular atrophy (SMA) is a genetic disorder characterized by a loss of spinal motor neurons. Patients carry a mutation in the SMN1 gene leading to low levels of the SMN protein. To better understand the cellular mechanism by which a lack of SMN protein leads to selective loss of motor neurons, I will study the role of the neuronal cytoskeleton in SMA mouse models. Firstly I want to investigate alterations in microtubule dynamics by time-lapse in vivo imaging of motor axons from SMA mice crossed to mice, which express EB3-YFP – a marker for dynamic microtubules. Secondly I will establish a new imaging tool based on fluorescent actin markers to study alterations of actin dynamics in SMA. If the cytoskeleton is indeed destabilized in SMA mice, a pharmacological treatment with microtubule stabilizing drugs will be used to test if there is a beneficial effect on disease progression.