We use a multidisciplinary approach (including evolutionary genomics, mouse genetics and embryology) to uncover the genetic changes that underlie human-specific brain development and function. Specifically we are focused on noncoding regulatory sequences called enhancers. We have identified several enhancers which have acquired rapid changes along the human lineage, and are active in the developing brain. Using transient transgenic assays in mice and iPSCs, we study the activity differences and functional impact of these enhancers upon brain development and behavior. We collaborate with Dr. Greg Wray, an evolutionary genomicist. A recent study describing the role of one of these loci, HARE5, was published in Current Biology and was featured in multiple news outlets! Please see our recent reviews in Bioessays, Current Opinion in Neurobiology to hear more about this exciting topic. Learn about this work on evolutionary-important enhancers published in Current Biology, with an interview with Debby on NPR!
Our most recent work uses mouse models and primate iPSCs to mechanistically understand how HARE5 influences neural progenitors. Please read about our exciting new discoveries, posted on bioRxiv. We show that HARE5 enhancer fine-tunes radial glia potency and neurogenesis to impact cortical expansion and function.
We continue to investigate molecular regulation of cortical evolution using mouse and human models.
