Researchers have found a genetic signature located exclusively in the nerve cells that supply, or innervate, the muscles of an organism’s outermost extremities: the hands and feet. This signature, observed in both mice and chicks, involves the coordinated activity of multiple genes, and is fundamentally distinct from cells innervating nearby anatomical regions, such as more proximal muscles in the limb. The findings suggest that the evolution of the extremities may be related to the emergence of fine motor control, such as grasping — one of biology’s most essential adaptations.
The study, led by neuroscientists at Columbia University’s Mortimer B. Zuckerman Mind Brain Behavior Institute and New York University, was published in the journal Neuron.
“The emergence of hands, feet and digits — about 400 million years ago — represented a turning point in evolution; it helped the first land animals perform a variety of fine motor skills, like grasping, which eventually gave rise to the complex motor abilities that we humans use every day — from typing on a keyboard to painting a work of art,” said Thomas M. Jessell, PhD, the paper’s senior author and codirector of Columbia’s Zuckerman Institute. “But while fine motor control has proven critical for survival for hundreds of millions of years, little was known about how the nerve cells that extend to the tips of our fingers and toes make these skills possible.”
For this study, the researchers focused on motor neurons, the class of nerve cells that guide movement. Motor neurons achieve this by innervating specific muscles, and then relaying signals from the brain about how those muscles should 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 muscles of the limb.”
Specifically, Mendelsohn observed that the motor neurons that supply both the hands and the feet did not produce a molecule called retinoic acid.
“One of the hallmark features of motor neurons is that they require retinoic acid for their growth and development,” said Mendelsohn. “But for some reason digit-innervating motor neurons weren’t producing it.”
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