The Stiles laboratory works on a pair of basic helix loop helix (bHLH) transcription factors known as Olig1 and Olig2. Within the bHLH gene targeting domain the Olig proteins are virtually identical to each other but their amino acid sequences diverge significantly in the amino and carboxy terminal domains. The two Olig genes are colocalized to within 40 Kb of each other on human chromosome 21 within the Down syndrome critical region suggesting that they might contribute to the neurological and cognitive defects associated with that syndrome. In accord with this notion, overexpression of Olig1 in neural progenitor cells of the developing telencephalon triggers early postnatal neuronal cell death similar to that observed in humans with trisomy 21. Current work in the Stiles lab is aimed at identifying genetic targets of the two Olig gene products and understanding the post translational mechanisms that regulate their function.
