Harnessing Natural Cellular Variability to Understand How Alternative Splicing Controls Neuronal Polarity

Neurons are exceptionally polar – their different parts possess utterly distinct structural and functional attributes. Axons and dendrites are two such polar specialisations, whose segregation early in development depends upon alternative splicing (AS) of key mRNAs. How AS contributes to the subsequent maintenance of neuronal polarity, however, remains unknown. To answer this question, this project will use state-of-the-art bioinformatic, molecular and neurophysiological tools at the single-cell level. We will leverage natural variation within a distinct neuronal population to understand how AS can influence neuronal polarity across time and space, gaining fundamental insight into processes that are crucial for normal brain function.