Squaring the circle: The expression and function of axon guidance circular RNAs during neuronal development

Abstract

In this thesis we investigated the expression and function of axon guidance circular RNAs (circRNAs) in the developing (mouse) brain. We tested and optimized various assays to measure, label and overexpress or knockdown axon guidance circRNAs using RNA-seq, RT-qPCR, Nanostring and (sm)(F)ISH to study the spatiotemporal expression of a selected group of axon guidance circRNAs and we adapted various manipulation tools to investigate their function in vitro and in vivo. Our major findings are that axon guidance circRNAs i) are conserved between human and mice, ii) are dynamically expressed throughout the mammalian brain over the course of development, iii) reveal expression peaks in the mouse cortex before birth, iv) show age-related accumulation, v) are expressed in excitatory cells, vi) have no expression in glia and vii) are upregulated after cellular activation. These findings increase our understanding on axon guidance circRNA expression and function, but further studies are necessary to elucidate the exact function(s) of each axon guidance circRNA in neuronal development and their role(s) in neurological disease.