Scientists at the University of Wisconsin-Madison have found that a single gene guides the development of all cells in the human brain and central nervous system, a discovery that sheds light on what distinguishes our brains from those of otherspecies and opens a promising avenue toward possible treatment of diseases such as Alzheimer's and Parkinson's.
Su-Chun Zhang, a professor of anatomy and neurology at UW who led the new study, said knowledge of this special gene, called a master regulator, may allow scientists to create a large bank of early brain stem cells, "so you can create any kind of neurons or glial cells in the brain or spinal cord." For example, the technique could allow scientists to generate dopamine-generating neurons to replace those lost in Parkinson's disease.
The finding also raises the possibility that researchers may be able to rejuvenate brain stem cells inside the body rather than in a lab dish in order to repair damage from disease.
"We are heading in that direction," Zhang said.
Writing in the journal Cell Stem Cell, Zhang and his colleagues described the gene, Pax6, which plays a role in the development of the eye and pancreas in mice and other species.
But the UW team found that in humans the gene is present much earlier than in other species, guiding the most primitive brain and nervous system cells toward their specific jobs. The gene appears to be so critical to human development that human embryos do not develop without it and a mutation in the gene causes major defects in brain structure.
"I think it's a very significant paper," said Shekar Kurpad, associate professor of neurosurgery at the Medical College of Wisconsin, who wasn't involved in the study. "It has enormous implications in various studies of neurologic disease."
Among other insights, the discovery reveals the limitations of using mice and other animals as models for understanding what happens in the human brain, Kurpad said.
Zhang, who has been studying development of the brain and nervous system from human stem cells for more than a decade, began looking into the gene after discovering that it was expressed in all human neural stem cells. In a previous study, Zhang and his colleagues showed that the primitive brain cells of rhesus monkeys also showed very early expression of the Pax6 gene.
Scientists knew that when animals do not have the gene, they do not develop eyes and have a much thinner-than-normal cerebral cortex. In humans, the cerebral cortex is considered the center of intelligence and is crucial to memory, thought, language, vision and hearing.
Kurpad said the discovery of the role Pax6 plays in human brain development could help answer other developmental questions.
"Conceptually this study not only makes a real stride in explaining how the nervous system develops," he said, "but also carries implications about how other systems may develop."
