Presentation description

Microcephaly is a developmental disorder in which a baby is born with a small head due to atypical brain development. Using exome sequencing from a cohort of human patients with microcephaly, we identified a list of candidate disease-genes. Relevant orthologs in Drosophila melanogaster, or fruit fly, were identified and tested for brain size defects. From this effort, we found that Imp, an RNA binding protein, is required for brain development and neuronal function. When Imp was knocked down in neurons using RNAi, animals demonstrated seizures and smaller brain sizes. RNA binding proteins regulate RNA metabolism by affecting splicing, transport, stability, and protein translation, but the molecular mechanism of how Imp regulates its targets during neurodevelopment is not known. We aim to determine how Imp functions in neurons and its involvement in brain formation and function. Since two of Imp's mRNA targets, Sap47 and Sdc, have many isoforms, we tested whether Imp affects splicing. These genes, when knocked out in neurons in the fly, were also found to cause a small brain phenotype and seizures, respectively. Ongoing research will determine whether Imp also plays a role in mRNA stability. In the future, this research will help us to better understand neurodevelopmental disorders such as microcephaly and identify drugs to help alleviate accompanied symptoms of microcephaly such as seizures.