Scientists at the Salk Institute have discovered that the development of neurons — which are responsible for specific tasks in the brain — is much more flexible than previously believed.
By studying sensory neurons in mice, the Salk team found that the malfunction of a single molecule can prompt the neuron to make a switch in its development, changing a neuron originally destined to process sound or touch, for example, to instead process vision.
The finding, reported Monday in the Proceedings of the National Academy of Sciences, will help neuroscientists better understand how brain architecture is molecularly encoded and how it can become miswired. It may also point to ways to prevent or treat human disorders such as autism that feature substantial brain structure abnormalities.
The mechanism, a transcription factor called Lhx2 that was inactivated in neurons, can be used to switch genes on or off to change the function of a sensory neuron in mice.
“This proess happens while the neuron matures and no longer divides. We did not understand before this study that relatively mature neurons could be reprogrammed in this way,” said senior author Dennis O’Leary, Salk professor and holder of the Vincent J. Coates chair in molecular neurobiology.
“This study provides proof that the brain is very plastic and that it responds to both genetic and epigenetic influences well after birth,” says O’Leary. “Clinical applications for brain disorders are a long way away, but we now have a new way to think about them.”
However, the findings may be an ingredient that contributes to the success of early intervention in some very young children diagnosed with autism, said Andreas Zembrzycki, a senior research associate at Salk. “The brain’s wiring is determined genetically as well as influenced epigenetically by environmental influences and early intervention preventing brain miswiring may be an example of converging genetic and epigenetic mechanisms that are controlled by Lhx2,” he said.
The work was funded by the National Institutes of Health and a grant from the National Science Council of Taiwan.
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