Researchers at the Lieber Institute for Brain Development (LIBD), with colleagues, have conducted investigations with brain tissue from hundreds of donated human brains, across races and stages of life, to examine the role of genetics and gene expression in shaping the prefrontal cortex region (PFC) of the brain and how it functions throughout life. The PFC regulates complex cognitive, emotional and behavioral functions that are considered particularly human. Healthy functioning of this region is believed to be compromised in several neurological and psychiatric disorders, including schizophrenia and autism spectrum disorder.
The research team, including scientists from LIBD, the National Institute of Mental Health, Johns Hopkins and Illuminato Biotechnology, Inc., identified gene expression (“transcription”) changes during human fetal development that get reversed in healthy brain development in very early life, and then 50 years later those same reversals occur again in the ageing brain. They also found a strikingly similar molecular architecture in the PFC, irrespective of genetic differences across individuals and races. They comment that the human genome appears to create this consistent architecture despite millions of genetic differences across individuals and races, and they suggest that it might be necessary to consider how each individual, complete genome is affected by evolution and the environment and “acts” as a whole (in development, biological function and disease). Their findings were published in the journal Nature on October 27, 2011.
They suggest that it might be necessary to consider how each individual, complete genome is affected by evolution and the environment and “acts” as a whole (in development, biological function and disease).
The researchers used genome-wide DNA and RNA analyses of 269 human brain specimens to produce a comprehensive view of gene expression from fetal development through late life in the PFC. Through this thorough analysis of gene expression in brain tissue, they discovered potentially novel mechanisms in the early development of the PFC that guide how neurons develop, get patterned, regenerate and differentiate.
The research team has made the DNA and RNA datasets from this study freely available via the online Braincloud app.
Carlo Colantuoni, Ph.D., Investigator at LIBD and first author on the paper, comments that “this research is being greatly expanded to explore many more human brain samples in health and neuropsychiatric disorders across the lifespan. Critically, this data in human brain development is being further leveraged by integration with data from pluripotent stem cells that we can study experimentally in the laboratory. We are now working to show how the cells from individuals whose brain tissue we have studied reflect the unique biology of that person’s genome throughout life, and in particular how cells from each individual differ as they begin to construct the brain.”