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Gene 'switch' clues us to origins of fine motor skills
Researchers have identified a genetic signature found exclusively in nerve cells that innervate muscles in our hands and feet. This gene signature is seeen in both mice and chickens, and involves coordination between multiple genes.
Neuroscientists at Columbia University's Mortimer B. Zuckerman Mind Brain Behavior Institute, along with those of New York University, led the study published in the journal Neuron.
Researchers focused on motor neurons, a class of nerve cells that guide movement. Motor neurons target specific muscles, then relay signals from the brain telling those muscles how to move. The motor neurons that guide movement of the digits are called digit-innervating motor neurons.
"When we began this research, we were simply looking to compare key molecular features — namely gene activity — in motor neurons that supply different muscles in the leg," said Alana Mendelsohn, an MD/PhD candidate at Columbia and the paper's first author. "Instead, it soon became clear that the pattern of gene activity in the digit-innervating motor neurons in the foot was strikingly different compared to activity of motor neurons that innervate the more proximal [situated nearer to the center] muscles of the limb."
Specifically, Mendelsohn saw that motor neurons that supply both hands and feet did not produce a molecule called retinoic acid.
In fact, experiments reveal that retinoic acid, in digit-innervating motor neurons, is harmful. When the team introduced retinoic-acid into mouse and chick embryos, digit-innervating motor neurons stopped developing.
To investigate, Columbia researchers teamed up with Jeremy Dasen PhD, a former post-doctoral fellow with Dr. Jessell and now professor of neuroscience at the NYU Neuroscience Institute and an expert in the development and evolution of motor circuits.
"The low levels of Hoxc9 appeared to be particularly important," said Dr. Jessell, who is also the Claire Tow Professor of Motor Neuron Disorders in the departments of neuroscience and biochemistry and molecular biophysics at Columbia University Medical Center. "Hoxc9 activity was high enough to prevent the production of retinoic acid (which would have been harmful) but low enough to still allow for the production of other proteins that we think are also necessary for the complete formation of digit-innervating motor neurons."
Moving forward, researchers hope to identify more in the suite of genes and proteins involved in digit-innervating motor neuron development. Also, they want to further investigate how the nervous system adapts to the emergence of digits over evolutionary history.
This paper is titled: "Divergent hox coding and evasion of retinoid signaling specifies motor neurons innervating digit muscles."
This research was supported by The National Institutes of Health (R01 NS062822, R01 NS033245), the Brain Research Foundation, the Harold and Leila Y. Mathers Foundation, Project A.L.S. and the Howard Hughes Medical Institute.
The authors report no financial or other conflicts of interest.
Columbia University's Mortimer B. Zuckerman Mind Brain Behavior Institute brings together an extraordinary group of world-class scientists and scholars to pursue the most urgent and exciting challenge of our time: understanding the brain and mind. A deeper understanding of the brain promises to transform human health and society. From effective treatments for disorders like Alzheimer's, Parkinson's, depression and autism to advances in fields as fundamental as computer science, economics, law, the arts and social policy, the potential for humanity is staggering. To learn more, visit: zuckermaninstitute.columbia.edu.
For some unknow reason, retinoic acid, in digit-innervating motor neurons, is harmful.
Image Credit: studyblue.com