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Nature. 2014 Apr 10;508(7495):199-206. doi: 10.1038/nature13185. Epub 2014 Apr 2.

Transcriptional landscape of the prenatal human brain.

Author information

1
1] Allen Institute for Brain Science, Seattle, Washington 98103, USA [2].
2
Allen Institute for Brain Science, Seattle, Washington 98103, USA.
3
Division of Genetic Medicine, Department of Pediatrics, University of Washington, 1959 North East Pacific Street, Box 356320, Seattle, Washington 98195, USA.
4
1] Department of Radiology, Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA [2] Computer Science and AI Lab, MIT, Cambridge, Massachusetts 02139, USA.
5
Department of Neurobiology and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, Connecticut 06510, USA.
6
Department of Radiology, Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
7
1] Program in Computational Biology and Bioinformatics, Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA [2] Department of Computer Science, Yale University, New Haven, Connecticut 06520, USA.
8
Program in Neurogenetics, Department of Neurology and Semel Institute David Geffen School of Medicine, UCLA, Los Angeles, California 90095, USA.
9
1] Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington 98101, USA [2] Department of Neurological Surgery, University of Washington School of Medicine, Seattle, Washington 98105, USA.
10
Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas 75390, USA.
11
Zilkha Neurogenetic Institute, and Department of Psychiatry, University of Southern California, Los Angeles, California 90033, USA.
12
1] Department of Pediatrics, Children's Hospital, Los Angeles, California 90027, USA [2] Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.

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.

PMID:
24695229
PMCID:
PMC4105188
DOI:
10.1038/nature13185
[Indexed for MEDLINE]
Free PMC Article
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