Translational regulation of cerebral cortex wiring

The mammalian cerebral cortex is a highly complex brain structure containing a wide diversity of neuronal cell types interconnected in a remarkably specific manner. The many behaviours observed in mammals rely on the precise assembly and fine-tuning of this connectivity, so understanding the molecular mechanisms that govern its development is a major scientific challenge. Neurons use dedicated transcriptional programmes to establish their connectivity, but in eukaryotes, post-transcriptional events control gene expression patterns and mediate key regulatory steps to eventually dictate cell function. However, it is yet unclear to what extent post-transcriptional mechanisms are involved in the formation of cortical networks. The goal of this proposal is to investigate the role of translation regulation in establishing neuronal connectivity during mouse cortical development, by studying two major processes that coordinate an effective and specialised translation: mRNA modifications and ribosome specialisation. We will address how these processes are differentially regulated in neuronal cell types for their integration into cortical networks, and how they are temporally regulated by changes in cortical dynamics during critical postnatal developmental stages. This will highlight how the refinement of transcriptional programmes by translation instructs cortical connectivity development.