Roles of enhancer SINEs during mouse cortical development (360G-Wellcome-109052_Z_15_A)

Mammalian brain development relies on the sequential generation of neurons that form the cortical and subcortical structures. Spatiotemporal control of cell behaviours and sequential production of neurons expressing layer-specific genes is achieved through tight control of transcription. The Riccio laboratory recently identified a subset of Short Interspersed Elements (SINEs) that control the expression of activity-regulated genes in cortical neurons. We discovered that these specific SINEs function as enhancers, and are transcribed from their internal RNA Polymerase III promoters to produce enhancer RNAs (eRNA). Importantly, SINE eRNA is necessary for enhancing the expression of RNAPII-dependent genes proximal to enhancer SINEs in the genome. It has been reported that specific SINEs can recapitulate expression patterns of neuronal genes and, through evolution, may have gained new functions as developmentally regulated enhancers. In this project I will select candidates from the enhancer SINEs previously identified by the Riccio laboratory and characterise their role in cortical development. The aims of my project are the following: To characterize eSINEs that regulate neural genes during cortical development, in vitro To analyse the role of selected eSINEs in cortical development using in utero electroporation Generation and analysis of a transgenic mouse lacking a selected eSINE