TY - JOUR TI - Regulation of ELAVL RNA binding proteins promotes neuronal diversity in the neocortex DO - https://doi.org/doi:10.7282/t3-rcw0-xs37 PY - 2021 AB - The diversity of neurons in the neocortex endows that structure with its wide range of abilities. It is likely the interplay of proteins on extracellular, transcriptional, and post-transcriptional levels that determines cell type diversity in the neocortex. Of these, post-transcriptional processes are especially important for the time sensitive steps of neuronal development. This thesis explores the mechanisms by which two RNA Binding Proteins (RBPs), in the Embryonic Lethal and Abnormal Vision Like (Elavl) protein family, promote diversity of neurons during neocorticogenesis. ELAVL1, also known as Hu antigen R (HuR), is a ubiquitously expressed RBP. We found that HuR binds over 7,000 targets during neocortical development. Specifically, it discriminates between Foxp1 and Foxp2 mRNA targets to define the respective identities of those two subpopulations of neocortical pyramidal neurons. Additionally, I discovered that phosphorylation sites throughout mouse HuR/ELAVL1 likely regulate target discrimination. In addition to phosphorylation sites on RBPs, alternative 3’ and 5’ untranslated regions (UTRs) can allow for target discrimination by RBPs. Within the embryonic mouse neocortex, we found a wide-spread pattern of repression and derepression of mRNA translation. I found that specific isoforms of the Hu antigen D (HuD/ELAVL4) RBP are repressed by the CUG-binding protein 1/CUG-BP-Elav like family 1 (CUGBP1/CELF1) RBP up to embryonic day 16. CUGBP1/CELF1 is able to discriminate amongst HuD/ELAVL4 isoforms through its alternative 5’UTRs. In sum, the ability to differentiate among RNA transcripts directly leads to an RBP’s role in determining cellular diversity through subpopulation identity. Regulation of RBPs, at the post-translational level through phosphorylation and at the post-transcriptional level through alternative 5’utrs, promotes neocortical cell type diversity. KW - Neuroscience KW - Neuroscience LA - English ER -