Molecular and cell biological mechanisms mediating re-establishment and maintenance of cell polarity in the developing CNS

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Newborn neurons in the spinal cord of the developing embryo shed their tips to move to their final location. As a result of this shedding event, these newborn neurons lose key proteins that allow them to distinguish their front from their back, causing them to lose polarity. Following this, the neuron must now rapidly repolarise itself. This repolarisation is crucial, as it allows the neuron to extend a long cell-process, called an axon, which makes connections with its targets, which could be muscles or other neurons. In the developing embryo, the neuron repolarises in response to external signals from the surrounding tissue. These external cues determine the position of this repolarisation and therefore determine the direction in which the axon will travel, or if it forms at all. This is thus a critical event that is essential for the formation of functional neuronal circuitry. I propose to study the molecular and cellular mechanisms that direct this key cell-biological process, and a better understanding of this will ultimately lead to the possibility of manipulating and/or stimulating it to treat neural disorders during embryogenesis and adulthood. Additionally, many cancer cells also undergo a very similar repolarisation process during the process of metastasis, which allows them to migrate to different locations and form more tumours. It is likely that the cancer cells do this in a way similar to newborn neurons, so understanding neuron repolarisation will potentially also help us to understand how cancer cells migrate to form secondary tumours. Thus understanding how cells repolarise in response to surrounding tissues has far-reaching consequences.