Geneshift History Traced through the Mouse’s Evolving Brainscape
Much like geologic hotspots shape geography through space and time, genomic hotspots influence the structure of the developing brain. Even long-dormant geologic features and genes may leave behind patterns, stories of change that we might read—provided we learn an unfamiliar language.
The developing brain’s story is told not only in the form of genes, but also neurons. So bringing the story to light is an interdisciplinary effort, as the scientists at the Allen Institute for Brain Science can attest. These scientists have introduced the Developing Mouse Brain Atlas. According to Allan Jones, Ph.D., the Allen Institute’s CEO, the Atlas “works like a Rosetta stone for the developing brain.”
The Atlas traces the development of the mouse brain from the embryo to the adult, creating a preliminary genetic key that allows researchers to pinpoint the age and location of regions of the developing brain. This work lays the foundation for tracking regions of the mouse brain through development, which could have valuable implications for translational work in human brain developmental disorders.
To identify individual brain regions, and their age, researchers frequently turn to using genes that can be found exclusively in that particular region and time point. But truly specific so-called “marker” genes are actually quite rare, explained Michael Hawrylycz, Ph.D., investigator at the Allen Institute for Brain Science. “Rather than relying on single genes, we were able to identify combinations of genes and use those combinations to create a unique code that can be used to place regions of the brain in space-time,” explained Hawrylycz.
Research that led to the creation of the Atlas appeared June 19 in the journal Neuron, in an article entitled “A High-Resolution Spatiotemporal Atlas of Gene Expression of the Developing Mouse Brain.” The article describes how Allen Institute researchers created a resource comprising 434,946 images, seven reference atlases, an ontogenetic ontology, and tools to explore coexpression of genes across neurodevelopment.
The resource, which serves as an expansion of the original Allen Mouse Brain Atlas, identifies where genes are active in the brain over seven different ages, ranging from prenatal to adult. Rather than profiling every gene in the mouse genome, the researchers selected approximately 2,100 genes with particular importance in development, and used those to identify individual brain regions at different time points.
The article also describes how the research team captured evidence of how the brain develops from its earliest form of stacked primordial plates to its adult form with the more familiar geographic regions that begin to correspond to specialized functional divisions of the brain.
“We can now place this important organizational transition from plates to regions within developmental time,” concluded Carol Thompson, Ph.D., lead author of the Neuron article and scientific program manager at the Allen Institute. “We already knew this transition took place, but now we understand the mechanics behind it at a much more detailed, molecular level.”
The data from the Allen Developing Mouse Brain Atlas are publicly available through the Allen Brain Atlas data portal at www.brain-map.org.