This Is Your Brain on PDGFD

Don’t worry. It’s the big one.

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Comparison of brains from a mouse and a human (left and right, respectively). (Image courtesy of Jan Lui.)

March 3, 2015 

You and a mouse have a lot in common genetically. Deep down in your DNA 85% of the genes that make you, you, also make Mickey, Mickey. Why then are your brain and a mouse’s brain so very different?*

Unfortunately, all that genetic similarity makes it difficult for scientists to determine exactly why your brain is so sizable when compared with that of a mouse. To this end, neuroscientists at University of California, San Francisco have developed a new technique for studying the genetic differences in mouse and human brain development. Using this technique they have pinpointed a gene that contributes to human brain growth that is switched off in the mouse.

“If you look at the mouse you can learn a lot about the mechanisms that are evolutionarily conserved between the human and the mouse,” explains Dr. Jan Lui, lead author of the study, which appeared in Nature in November. “But these are not going to explain why the human is really big compared to the mouse.”

The researchers found their difference in radial glia, the stem cells that go on to produce neurons and some of the other myriad cell types that make up the largest part of the mature brains of both mice and men. To do so they first built a map of which genes are expressed in different parts of both human and mouse brains. They compared brains that were in their early stages of development—after they had begun to grow and take shape but before the radial glia had transformed into neurons.

The team then located 18 genes that were expressed by radial glia in humans but not in mice. One gene in particular stood out because it was already known to produce a protein responsible for stimulating growth, PDGFD.† They were then able to show that when this protein is removed from human neural stem cells in culture, their growth is halted, and when it is added to mouse neural stem cells in mice, their growth is promoted.

“We don’t want to claim is that this is the magic bullet that causes the human brain to be big and the mouse brain to be small,” adds Lui. There are many other genes and proteins that likely contribute to the size difference, and this is just one of them. Still they hope their method will be useful for locating other genes in these and other types of samples, and for comparing humans with other animals that are even more closely related. 

The scientists also only require a few unique specimens in order to build their genetic map. Lui believes that this means it will be useful for more than studying the brain. “I think that it is a method that can be useful to a lot of different people and for a lot of different tissues, particularly unique cancer samples. You can learn about the internal cell composition of a tumor just from one sample.”

From: J.H. Lui, T. J Nowakowski, A.A. Pollen, A. Javaherian, A.R. Kriegstein, and M.C. Oldham; “Radial glia require PDGFD-PDGFRβ signaling in human but not mouse neocortex;” Nature, (2014) 315, 264-268; doi: 10.1038/nature13973

 *And very different they are: in size, in shape, in the amount of time they take to develop, in the number of connections between their neurons, and in the number of connections between their different parts. 
† PDGFD stands for “platelet derived growth factor D.”

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