Findings have significant implications for the prediction of drug side-effects.
The Allen Institute for Brain Science reported a series of findings that shed light on the structural and cellular complexity of the brain and could improve the understanding of side effects of therapeutics. Reported in Nature Online, the paper reports new subregions of known brain structures, reveals novel markers for major classes of brain cells, and documents the complexity of gene expression patterns in the brain.
“This landmark paper represents the first attempt to see what we can learn from a global analysis of gene expression across the entire brain,” notes Marc Tessier-Lavigne, Ph.D., chairman of the Allen Brain Atlas scientific advisory board and senior vp, research drug discovery at Genentech.
The study was based on a global analysis of gene expression using the Allen Brain Atlas. This atlast is a web-based, 3-D map of gene expression in the mouse brain detailing expression of more than 21,000 genes at the cellular level.
The findings indicate an extraordinary degree of heterogeneity in the brain. Although 80% of all genes are expressed in the brain, most genes are expressed in relatively few cells. Only a small fraction of all genes are expressed at high levels in all cells in the brain, whereas 75% of the genes are each expressed in fewer than 20% of the cells in the brain. In addition, gene expression patterns across brain regions show variable degrees of restriction to single brain structures.
The discovery that gene expression is often not regional has significant implications for understanding and predicting side-effects of therapeutic drugs. Such drugs act through specific proteins, which are built from expressed genes. The ideal drug would target a protein whose associated gene is expressed only in the regions affected by disease.
“Moving forward, we will continue to conduct research using the Allen Brain Atlas with a particular interest in the neocortex,” says Allan Jones, Ph.D., the Allen Institute’s CSO.