Post-transcriptional regulation in corticogenesis: how RNA-binding proteins help build the brain.

The cerebral cortex, the brain structure responsible for our higher cognitive functions, is built during embryonic development in a process called corticogenesis. During corticogenesis, neural stem cells generate distinct populations of progenitors and excitatory neurons. These new neurons migrate radially in the cortex, eventually forming neuronal layers and establishing synaptic connections with other neurons both within and outside the cortex. Perturbations to corticogenesis can result in severe neurodevelopmental disorders, thus emphasizing the need to better understand molecular regulation of brain development. Recent studies in both model organisms and humans have collectively highlighted roles for post-transcriptional regulation in virtually all steps of corticogenesis. Genomic approaches have revealed global RNA changes associated with spatial and temporal regulation of cortical development. Additionally, genetic studies have uncovered RNA-binding proteins (RBPs) critical for cell proliferation, differentiation, and migration within the developing neocortex. Many of these same RBPs play causal roles in neurodevelopmental pathologies. In the developing neocortex, RBPs influence diverse steps of mRNA metabolism, including splicing, stability, translation, and localization. With the advent of new technologies, researchers have begun to uncover key transcripts regulated by these RBPs. Given the complexity of the developing mammalian cortex, a major challenge for the future will be to understand how dynamic RNA regulation occurs within heterogeneous cell populations, across space and time. In sum, post-transcriptional regulation has emerged as a critical mechanism for driving corticogenesis and exciting direction of future research.