How do fingers type these words?
How do eyes read them?
How does the mouth speak, the tongue taste, the skin feel?
The simple answer is neurons. The connections between neurons regulate everything from reflexes and senses to learning and memory, as well as cognition. But how do neurons interact so the human body functions properly?
“We’re interested in how neurons form connections,” said Kristy Welshhans, Assistant Professor of Biological Sciences in the College of Arts and Sciences. “During development, first the neurons are born, but then they have to connect to one another.”
Neurons connect with one another through long processes, called axons. During development, though, how does the axon of a particular neuron know where to go?
At the tips of axons lie the answer and Welshhans’ primary research focus: the growth cone.
“The growth cone guides the axon to whatever it needs to connect with,” she said. “Our research focuses on point contacts, which are the adhesion points of the growth cone. Point contacts are necessary for connections between neurons to be made properly.”
Point contacts link the extracellular matrix and the cellular cytoskeleton — what Welshhans calls the “bones of the cell.”
Still, what tells a growth cone how to find its point of connection?
“Growth cones sense cues in the environment, which are similar to street signs and stop lights, that tell them where to go and what to connect with,” Welshhans said.
These cues can take the form of proteins made in the growth cone at point contacts. The proteins that are manufactured specifically within growth cones are the focus of the three-year, $375,000 grant Welshhans received in 2016 from the National Institutes of Health — entitled, “Molecular mechanisms regulating local translation during axon growth and guidance.”
One of the most important proteins is beta-actin, which is part of the cellular cytoskeleton and necessary to direct the growth cone to its target.
“Our studies have focused on understanding how other proteins work together to support the translation of beta-actin,” Welshhans said.
That’s only part of her work, though. Understanding how connections are made during development also provides insight into neurodevelopmental disorders like Down Syndrome — the other half of Welshhans’ research.
“If we understand how development proceeds normally, we can apply that knowledge to further our understanding of what happens in conditions like Down Syndrome,” she said.
One of the proteins made inside the growth cone is DSCAM (Down Syndrome Cell Adhesion Molecule). When the axon produces too much DSCAM, which is what happens in Down syndrome, the axons are much shorter than they should be.
“As a result, developing axons may not make the correct connections, which can contribute to the intellectual disability that is observed in individuals with Down Syndrome,” Welshhans said.
Overall, the mission of her basic and translational (Down Syndrome-focused) research is the same: to identify the role of proteins involved in axon growth, which can inform the development of genetic or pharmacological treatments for neurological disorders.