"Neurodegenerative diseases typically effect a specific population of neurons, leaving many others untouched. For example, in ALS it is corticospinal motor neurons in the brain and motor neurons in the spinal cord, among the many neurons of the nervous system, that selectively die," Arlotta said. "What if one could take neurons that are spared in a given disease and turn them directly into the neurons that die off? In ALS, if you could generate even a small percentage of corticospinal motor neurons, it would likely be sufficient to recover basic functioning," she said.
The experiments that led to the new finding began five years ago, when "we wondered: in nature you never seen a neuron change identity; are we just not seeing it, or is this the reality? Can we take one type of neuron and turn it into another?" Arlotta and Rouaux asked themselves.
Over the course of the five years, the researchers analyzed "thousands and thousands of neurons, looking for many molecular markers as well as new connectivity that would indicate that reprogramming was occurring," Arlotta said. "We could have had this two years ago, but while this was a conceptually very simple set of experiments, it was technically difficult. The work was meant to test important dogmas on the irreversible nature of neurons in vivo. We had to prove, without a shadow of a doubt, that this was happening."
The work in Arlotta's lab is focused on the cerebral cortex, but "it opens the door to reprogramming in other areas of the central nervous system," she said.
Arlotta, an HSCI principal faculty member, is now working with colleague Takao Hensch, of Harvard's Department of Molecular and Cellular Biology, to explicate the physiology of the reprogrammed neurons, and learn how they communicate within pre-existing neuronal networks.
"My hope is that this will facilitate work in a new field of neurobiology that explores the boundaries and power of n
|Contact: Paola Arlotta |