Transcriptional landscape of the prenatal human brain

Jeremy A. Miller, Song Lin Ding, Susan M. Sunkin, Kimberly A. Smith, Lydia Ng, Aaron Szafer, Amanda Ebbert, Zackery L. Riley, Joshua J. Royall, Kaylynn Aiona, James M. Arnold, Crissa Bennet, Darren Bertagnolli, Krissy Brouner, Stephanie Butler, Shiella Caldejon, Anita Carey, Christine Cuhaciyan, Rachel A. Dalley, Nick DeeTim A. Dolbeare, Benjamin A C Facer, David Feng, Tim P. Fliss, Garrett Gee, Jeff Goldy, Lindsey Gourley, Benjamin W. Gregor, Guangyu Gu, Robert E. Howard, Jayson M. Jochim, Chihchau L. Kuan, Christopher Lau, Chang Kyu Lee, Felix Lee, Tracy A. Lemon, Phil Lesnar, Bergen McMurray, Naveed Mastan, Nerick Mosqueda, Theresa Naluai-Cecchini, Nhan Kiet Ngo, Julie Nyhus, Aaron Oldre, Eric Olson, Jody Parente, Patrick D. Parker, Sheana E. Parry, Allison Stevens, Mihovil Pletikos, Melissa Reding, Kate Roll, David Sandman, Melaine Sarreal, Sheila Shapouri, Nadiya V. Shapovalova, Elaine H. Shen, Nathan Sjoquist, Clifford R. Slaughterbeck, Michael Smith, Andy J. Sodt, Derric Williams, Lilla Zöllei, Bruce Fischl, Mark B. Gerstein, Daniel H. Geschwind, Ian A. Glass, Michael J. Hawrylycz, Robert F. Hevner, Hao Huang, Allan R. Jones, James A. Knowles, Pat Levitt, John W. Phillips, Nenad Šestan, Paul Wohnoutka, Chinh Dang, Amy Bernard, John G. Hohmann, Ed S. Lein

Research output: Contribution to journalArticle

Abstract

The anatomical and functional architecture of the human brain is mainly determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of the mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high-resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser-microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and post-mitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and outer subventricular zones even though the outer zone is expanded in humans. Both germinal and post-mitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in the frontal lobe. Finally, many neurodevelopmental disorder and human-evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development.

Original languageEnglish (US)
Pages (from-to)199-206
Number of pages8
JournalNature
Volume508
Issue number7495
DOIs
StatePublished - Apr 10 2014
Externally publishedYes

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ASJC Scopus subject areas

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Cite this

Miller, J. A., Ding, S. L., Sunkin, S. M., Smith, K. A., Ng, L., Szafer, A., Ebbert, A., Riley, Z. L., Royall, J. J., Aiona, K., Arnold, J. M., Bennet, C., Bertagnolli, D., Brouner, K., Butler, S., Caldejon, S., Carey, A., Cuhaciyan, C., Dalley, R. A., ... Lein, E. S. (2014). Transcriptional landscape of the prenatal human brain. Nature, 508(7495), 199-206. https://doi.org/10.1038/nature13185