The human cerebral cortex contains 16 billion neurons, wired together into arcane, layered circuits responsible for everything from our ability to walk and talk to our sense of nostalgia and drive to dream of the future. In the course of human evolution, the cortex has expanded as much as 1,000-fold, but how this occurred is still a mystery to scientists.

Now, researchers at UC San Francisco have succeeded in mapping the genetic signature of a unique group of stem cells in the human brain that seem to generate most of the neurons in our massive cerebral cortex.

The new findings, published Sept. 24, 2015 in the journal Cell, support the notion that these unusual stem cells may have played an important role in the remarkable evolutionary expansion of the primate brain.

"We want to know what it is about our genetic heritage that makes us unique," said Arnold Kriegstein, MD, PhD, professor of developmental and stem cell biology and director of the Eli and Edyth Broad Center of Regeneration Medicine and Stem Cell Research at UCSF. "Looking at these early stages in development is the best opportunity to understand our brain's evolution."

Building a Brain from the Inside Out

The grand architecture of the human cortex, with its hundreds of distinct cell types, begins as a uniform layer of neural stem cells and builds itself from the inside out during several months of embryonic development.

Until recently, most of what scientists knew about this process came from studies of model organisms such as mice, where nearly all neurons are produced by stem cells called ventricular radial glia (vRGs) that inhabit a fertile layer of tissue deep in the brain called the ventricular zone (VZ). But recent insights suggested that the development of the human cortex might have some additional wrinkles.