Understanding of Human Brain’s Uniqueness
April 28th 2011 06:53
Stem cells in the human brain spin off neurons that populate the layers of the cerebral cortex and form vertical columns.
Image credit Kenneth X. Probst
Scientists are making great strides in figuring out how the human brain – with its expansive cerebral cortex and corresponding capacity for higher thinking – became one of nature’s greatest wonders. Insights about how the brain develops are leading to novel ideas about the causes of a range of brain disorders, and are raising hopes for the regeneration of tissue that is lost in diseases such as Alzheimer’s. At the center of this scientific ferment are new stem cell discoveries by researchers at UCSF.
Stem Cells Drive Expansion of Brain’s Cortex
Like the phyllo dough crust in baklava and certain other Greek and Middle Eastern delicacies, the reptilian and mammalian cortices are made from thin layers. In reptiles, the cortex has three layers; in mammals, it has six. The entire cortex is about two millimeters thick.
While human brains have the same six cortical layers as brains from less well-equipped mammals, these sheets of cortical brain matter extend outward much farther in humans. Furthermore, in Homo sapiens and other primates, the cortex folds many times. The folding allows more neural circuitry to fit into the skull and gives the human brain its unique architecture and cauliflower-like appearance.
“The human brain has an enormously expanded surface area in the cerebral cortex,” says Arnold Kriegstein, MD, PhD, director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF. Like the abundance of chips and transistors in a supercharged computer, all those added neurons form more circuits, allowing for more computation and more sophisticated kinds of processing. For us, the payoff is conscious thought, reasoning and language – and the wherewithal to build rich civilizations that span the globe.
Arnold Kriegstein, MD, PhD
Last year, Kriegstein’s laboratory team reported the identification of a long-elusive stem cell that we may have to thank for our success as a species. The stem cell appears to be responsible for the explosive growth of neurons that occurs in a part of the fetal primate brain known as the outer subventricular zone (OSVZ).
If the neurons in the brain were like people in a metropolis, the fetal brain’s mid-gestational growth spurt in the OSVZ would be like the suburban population boom on the outskirts of cities in the late 1900s.
Each time the OSVZ neural stem cell divides, it regenerates itself and also spins off an intermediary cell. These intermediary cells, in turn, divide many times to produce specialized neurons. Each stem cell sends a branch upward through the layers of cortex, and this extension acts like a guide wire for newborn neurons traveling through the cortical layers.
“There is a whole region that’s found in the human brain, but not in the rodent, where cells are born and delivered to the developing layers of the cortex,” Kriegstein says. “The newly described stem cells are responsible both for making the nerve cells and for guiding them to their proper locations in the cortex, where they form cell columns.”
As in all regions of the cortex, the neurons in these vertical columns form electrical circuits, and myriad columns are aligned horizontally throughout the plane of the cortex. The recently discovered OSVZ stem cell and its progeny appear to drive growth outward from the edges of this horizontal plane, Kriegstein says.
Evolution from Mouse to Human
Although the OSVZ region is absent in the mouse, Kriegstein’s lab team nonetheless went looking in the mouse brain for a stem cell similar to the OSVZ stem cell. They found it, but only in small numbers. Furthermore, in the mouse, these stem cells do not spin off the intermediate progenitors that powerfully amplify the growth of new neurons in the human brain.
This time-lapse movie shows cell division in a newly discovered type of brain stem cell in the mouse. The stem cell is similar to a human stem cell identified by the same UCSF laboratory research group last year. The cell nucleus moves in an unusual way, the researchers found. The movements may influence development within the brain’s cerebral cortex in ways that are not yet well understood. Images were acquired every 10 minutes. The playback rate is seven frames per second.
Credit: Xiaoqun Wang
This time-lapse movie shows a different type of unusual movement observed in another type of dividing stem cell in the
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