Researchers investigating why some people suffer from motor disabilities report they may have dialed back evolution’s clock a few ticks by blocking molecular pruning of sophisticated brain–to–limb nerve connections in maturing mice. The result was mice with enhanced manual dexterity that grab and eat food much faster than regular wild–type mice, according to a study published July 28 in the journal Science.

Scientists at Cincinnati Children’s Hospital Medical Center who led the study stress they aren’t trying to create a genetically superior species of rodents. They are testing the formation of nervous system connections during early development in genetically bred mouse models. Their goal is to understand how sophisticated nerve connections start to form in wild baby mice, disappear as the animals mature, and whether this information might one day help patients.

Their study points to a class of proteins called semaphorins, which control the formation of long thread–like nerves called axons and motor neuron connections in the mammalian corticospinal (CS) system. In particular the scientists identify a protein called PlexA1, a major receptor molecule that attracts semaphorins. Semaphorins prevent axons from forming in inappropriate regions of the nervous system.

In the case of mice – which spend most of their time on four paws – signaling between a semaphore protein called Sema6 and PlexA1 activates in young mice. This eliminates critical synaptic links between nerve cells to stop the formation of sophisticated CS neural connections and fine motor skills.

“We may have found a pivotal point in the evolution of the mammalian corticospinal (CS) system that leads to greater fine motor control in higher primates and people,” said Yutaka Yoshida, PhD, lead study investigator in the Division of Developmental Biology at Cincinnati Children’s. “Although we still need to explore this, it’s possible that some patients with motor disabilities have upregulated expression of PlexA1 or activated PlexA1 signaling that diminish cortico–motor–neuron connections and fine motor skills. Inhibition of PlexA1 signaling during childhood might be a way to restore these skills.”