The BrainSpan atlas of the developing human brain is designed as a foundational resource for studying transcriptional mechanisms involved in human brain development. Created by a research consortium supported by three ARRA-funded grants through the National Institutes of Health, the atlas consists of a variety of data modalities and data mining tools, to be augmented incrementally through its completion in late 2012.

Data and Tools

The BrainSpan atlas consists of the following features:

• A broad developmental survey of gene expression in specific brain regions using cutting-edge RNA sequencing and exon microarray techniques. These data provide unbiased coverage of the complete transcriptome in targeted cortical and subcortical structures across the full course of human brain development. Sixteen brain regions have been profiled in 42 brain specimens to date, spanning pre- and postnatal development in both males and females.
• Broad, high-resolution neuroanatomical transcriptional profiling spanning the entire prenatal human brain, generated using a combination of laser microdissection-based sample isolation and DNA microarrays. One complete specimen, comprised of approximately 300 distinct anatomical samples in the midgestational prenatal brain, is available to date.
• Cellular-resolution interrogation of transcript distributions in developing and adult human brain using a standardized high-throughput in situ hybridization (ISH) platform.
  • Postnatal developmental analysis of a set of genes and developmental stages designed to mirror the complementary NIH Blueprint Non-Human Primate (NHP) Atlas (www.blueprintnhpatlas.org). These data, along with the Allen Developing Mouse Brain Atlas (developingmouse.brain-map.org) enable direct phylogenetic comparisons of gene expression patterns in human, macaque, and mouse.
  • Analysis of disease-associated genes in the adult human brain, focused on brain regions clinically important for a variety of human neurodevelopmental disorders, including medial prefrontal cortex, primary visual cortex, hippocampus, amygdala and ventral striatum. Genes implicated in various neurological and neuropsychiatric diseases including autism, schizophrenia, epilepsy, Parkinson's disease, and Alzheimer's disease are included in this survey.
  • Cellular marker and key developmental gene analysis across the entire mid-gestational prenatal brain.
• Neuroimaging and histological reference atlases for different developmental stages to provide a neurodevelopmental and anatomical context for interpreting transcriptome data. These atlases will consist of high-resolution magnetic resonance imaging (MRI), multi-direction diffusion tensor imaging (DTI), and/or histological digital annotated reference atlases.
• A suite of Web-based tools will allow researchers to view, search and mine spatiotemporal gene expression patterns in the anatomical context of human brain development as well as link and integrate all data modalities.

These data and tools are designed to provide a valuable public resource for researchers, educators and medical communities for relating specific transcriptional programs to processes of normal human brain development and to facilitate translational research into human neurological disease.

Consortium Members

The BrainSpan atlas is being developed by a consortium consisting of the Allen Institute for Brain Science; Yale University (Nenad Sestan, Mark B. Gerstein); the Zilkha Neurogenetic Institute of the Keck School of Medicine of the University of Southern California (James A. Knowles, Pat Levitt); the Athinoula A. Martinos Center at Massachusetts General Hospital/Harvard Medical School and MIT HST/CSAIL (Bruce Fischl); and the University of California, Los Angeles (Daniel H. Geschwind), with strong collaborative support from the Genes, Cognition and Psychosis Program, which is part of the Intramural Research Program of NIMH, NIH (Thomas M. Hyde, Joel E. Kleinman, Daniel R. Weinberger).

Funding Support

This project was supported by Award Numbers RC2MH089921 (PIs: Ed Lein & Michael Hawrylycz, Allen Institute for Brain Science), RC2MH090047 (PI: James A. Knowles, University of Southern California) and RC2MH089929 (PI: Nenad Sestan, Yale University) from the National Institute of Mental Health. The content is solely the responsibility of the respective authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health.