Charting the Chemical Choreography of Brain Development

Diagram of the various parts of the brain of a six-week old embryo (Photo credit: Wikipedia)

 

 

 

 

 

From the 27 August 2013 Director’s blog item (National Institutes of Health)

 

Once in a while a research publication reveals an entirely new perspective on a fundamental issue in biology or medicine. Today’s blog is about such a paper. The story, though complex, is very significant.

The choreography of human brain development is amazing, but quite mysterious. Today’s post highlights a study [1] that reveals the locations of some of the chemical choreographers that collaborate with DNA to orchestrate these fancy moves in the brain.

This complex developmental dance starts in the womb as our brain cells arise, migrate to their proper locations, and mature. By the time we’re born, each of us has close to 100 billion of these cells, called neurons. But that’s not all. The brain also contains lots of other cell types—especially glia. Glial cells were previously thought to act primarily as servants to the neurons, but they’re actually more like partners. Our birth inventory is just the first act. Over the course of our lives, our experiences and environment continue to shape and re-shape the brain’s connections, albeit in varying paces and patterns.

The millions of chemical tags that modify or mark the genome tell it what to do, and when and where to do it. Taken together, we call this diverse collection of chemical cues the “epigenome.”

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Just as genetic mutations can lead to disease, glitches in DNA methylation may also trigger or increase the severity of brain disorders. Several studies have already linked abnormal methylation with disorders like schizophrenia, and conditions like Traumatic Brain Injury. This research is particularly exciting because these DNA methylation tags are not permanent. So, if we discover patterns of methylation that cause particular brain diseases, we can develop strategies to restore the healthy epigenetic profile—in effect, to bring those errant brain cells back in step with the dance of normal brain development.

Caption: Researchers mapped methylation sites in genomes of neurons and glia in the frontal cortex. mCH methyl tags, or non-CG methylation (purple stars), were absent at birth, but were added rapidly during the first few years of life and then more slowly until about age 30. After age 50, the number of mCH tags declined.
Credit: Eran Mukamel, Salk Institute

This study is a powerful example of how recent technological advances are revealing the secrets and complexities of the human brain—a process we hope to accelerate with the start of the BRAIN initiative!

References:

[1] Global epigenomic reconfiguration during mammalian brain development. Lister R, Mukamel EA, Nery JR, Urich M, Puddifoot CA, Johnson ND, Lucero J, Huang Y, Dwork AJ, Schultz MD, Yu M, Tonti-Filippini J, Heyn H, Hu S, Wu JC, Rao A, Esteller M, He C, Haghighi FG, Sejnowski TJ, Behrens MM, Ecker JR. Science. 2013 Aug 9;341(6146):1237905.

[2] Sequence data can be downloaded from National Center for Biotechnology Information GEO (GSE47966). The analyzed data is also available for browsing.

 

 Read the entire article here

 

 

 

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