Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States
Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States
Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States
Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States
Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States
Yurong Wang
Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States
Kenneth J Lim
Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States
Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States
Sarah J Morse
Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States
Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States
Tyler W Stradleigh
Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States
Erika Castillo Palacios
Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States
Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States
Spencer D Moss
Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States
Hannah Parolini
Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States
Diana Quintero
Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States
Diwash Shrestha
Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States
Daniel Vogt
Department of Pediatrics and Human Development, Grand Rapids Research Center, Michigan State University, Grand Rapids, United States
Leah C Byrne
Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, United States; Departments of Ophthalmology and Neurobiology, University of Pittsburgh, Pittsburgh, United States
Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, United States; Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States
Enhancers are cis-regulatory elements that play critical regulatory roles in modulating developmental transcription programs and driving cell-type-specific and context-dependent gene expression in the brain. The development of massively parallel reporter assays (MPRAs) has enabled high-throughput functional screening of candidate DNA sequences for enhancer activity. Tissue-specific screening of in vivo enhancer function at scale has the potential to greatly expand our understanding of the role of non-coding sequences in development, evolution, and disease. Here, we adapted a self-transcribing regulatory element MPRA strategy for delivery to early postnatal mouse brain via recombinant adeno-associated virus (rAAV). We identified and validated putative enhancers capable of driving reporter gene expression in mouse forebrain, including regulatory elements within an intronic CACNA1C linkage disequilibrium block associated with risk in neuropsychiatric disorder genetic studies. Paired screening and single enhancer in vivo functional testing, as we show here, represents a powerful approach towards characterizing regulatory activity of enhancers and understanding how enhancer sequences organize gene expression in the brain.
