This Is Your Brain on PDGFB

Don’t worry. It’s the big one.

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

Neuroscientists at University of California, San Francisco developed a new technique for studying the genetic differences in mouse and human brain development. Using this technique they pinpointed a gene that contributes to human brain growth that is switched off in the mouse.

You and a mouse have a lot in common. 85% of the genes that make you, you, also make Mickey, Mickey. This genetic similarity makes it difficult to determine why your brain and a mouse’s brain so different. And 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.

“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 turn into neurons and other cells that constitute the mature brains of both mice and men. To do so, they first built a map of the genes expressed in different parts of both human and mouse brains. They compared brains in an early stage of development, after they began to grow and take shape but before the radial glia turned into neurons.

The team located 18 genes that were expressed by radial glia in humans but not mice. One gene in particular stood out because it contains the instructions for a protein responsible for stimulating growth, PDGFD.† They then showed that when PDGFD 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 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 require only 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

† PDGFD stands for “platelet derived growth factor D.”