Journal Article

A comprehensive transcriptional map of primate brain development

Dolbeare, Tim A., Olson, Eric, White, Cassandra, Sodt, Andy J., Dee, Nick, Haradon, Zeb, Chapin, Mike, Gu, Guangyu, Ngo, Kiet, Gilbert, Terri L., Byrnes, Emi, Wohnoutka, Paul, Hevner, Robert F., Gibbs, Richard A., Lee, Felix, Butler, Stephanie, Fulfs, Erich, Sandman, David, Hawrylycz, Michael J., Potekhina, Lydia, Sjoquist, Nathan, Kuan, Chihchau L., Bernard, Amy, Parker, Patrick D., Mott, Erika, Chen, Jefferey, Rosen, David, Shapovalova, Nadiya, Reding, Melissa, Gee, Garrett, Roberts, Tyson, Gourley, Lindsey, Haynor, David R., Ebbert, Amanda, Nyhus, Julie, Caldejon, Shiella, Cate, Shelby, Hejazinia, Nika, Aiona, Kaylynn, Dotson, Nadia, Parry, Sheana, Jochim, Jay, Hohmann, John G., Gregor, Ben, May, Ryan, Miller, Jeremy A., Mastan, Naveed, Hall, Jon, Velasquez, Lissette, Mosqueda, Nerick, Royall, Joshua J., Townsend, Robbie, Bertagnolli, Darren, Ding, Song-Lin, Arnold, James, Parente, Jody, Luong, Lon, Sarreal, Melaine, Wagley, Udi, Lee, Chang-Kyu, Shapouri, Sheila, Pendergraft, Julie, Bennett, Crissa, Youngstrom, Brian L., Wu, Jennifer, Szafer, Aaron, Sunkin, Susan M., Shi, Shu, Hoerder-Suabedissen, Anna, Howard, Robert

2016

Overview

The transcriptional underpinnings of brain development remain poorly understood, particularly in humans and closely related non-human primates. We describe a high-resolution transcriptional atlas of rhesus monkey ( Macaca mulatta ) brain development that combines dense temporal sampling of prenatal and postnatal periods with fine anatomical division of cortical and subcortical regions associated with human neuropsychiatric disease. Gene expression changes more rapidly before birth, both in progenitor cells and maturing neurons. Cortical layers and areas acquire adult-like molecular profiles surprisingly late in postnatal development. Disparate cell populations exhibit distinct developmental timing of gene expression, but also unexpected synchrony of processes underlying neural circuit construction including cell projection and adhesion. Candidate risk genes for neurodevelopmental disorders including primary microcephaly, autism spectrum disorder, intellectual disability, and schizophrenia show disease-specific spatiotemporal enrichment within developing neocortex. Human developmental expression trajectories are more similar to monkey than rodent, although approximately 9% of genes show human-specific regulation with evidence for prolonged maturation or neoteny compared to monkey. A high-resolution gene expression atlas of prenatal and postnatal brain development of rhesus monkey charts global transcriptional dynamics in relation to brain maturation, while comparative analysis reveals human-specific gene trajectories; candidate risk genes associated with human neurodevelopmental disorders tend to be co-expressed in disease-specific patterns in the developing monkey neocortex. Gene expression in the primate brain Following the publication of the mouse and human brain gene expression atlases in recent years, Ed Lein and colleagues now present a high-resolution transcriptional atlas of pre- and post-natal brain development for the rhesus monkey — the dominant non-human primate model for human brain development and disease. The data charts global transcriptional dynamics in relation to brain maturation, while comparative analysis reveals human-specific gene trajectories; candidate risk genes associated with human neurodevelopmental disorders tend to be co-expressed in disease-specific patterns in the developing monkey neocortex.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/378/2571/2574 / 631/378/2571/2575 / 631/378/2583 / 631/378/2650 / 631/378/340 / Aging - genetics / Animal development / Animals / Autism Spectrum Disorder - genetics / Brain / Brain - cytology / Brain - embryology / Brain - growth & development / Brain - metabolism / Cell Adhesion / Conserved Sequence / Developmental biology / Female / Gene expression / Genetic aspects / Humanities and Social Sciences / Humans / Intellectual Disability - genetics / Macaca mulatta - genetics / Male / Mental disorders / Microcephaly - genetics / Monkeys & apes / multidisciplinary / Neocortex - embryology / Neocortex - growth & development / Neocortex - metabolism / Neurodevelopmental Disorders - genetics / Neurogenesis / Neurogenesis - genetics / Neurological disorders / Neurons / Physiological aspects / Primates / Risk Factors / Schizophrenia - genetics / Science / Spatio-Temporal Analysis / Species Specificity / Transcription, Genetic - genetics / Transcriptome