Summary: Research reveals molecular mechanism that allows neural networks to grow and branch.
Our nervous system is made up of billions of neurons that talk to each other through their axons and dendrites. As the human brain develops, these structures branch out in a wonderfully complex but poorly understood way that allows nerve cells to communicate and send messages throughout the body. Now, Yale researchers have discovered the molecular mechanism behind the growth of this complex system.
Their findings are published Advances in science.
Professor of Molecular Biophysics and Biochemistry and Professor of Physics Eugene Higgins, Ph.D. “Neurons are highly branched cells, and they are so because each neuron makes connections with thousands of other neurons,” says Joe Howard, the study’s researcher.
“We’re working on this branching process—how do branches form and grow? That’s what underlies the whole workings of the nervous system.”
The team studied the neuronal growth of fruit flies during their development from embryos to larvae. To visualize this process, they labeled neurons with fluorescent markers and imaged them under a spinning disk microscope. Because neurons are located only under the cuticle [outermost layer]researchers were able to observe this process in real time in live larvae.
After imaging neurons at different stages of development, the team was able to create time-lapse movies of growth.
At the earliest stages of development, sensory neurons begin with only two or three dendrites. But within five days, they had grown into large, tree-like structures with thousands of branches.
Analysis of dendritic tips revealed their dynamic and stochastic (randomly determined) growth, which alternates between growing, shrinking, and paused states.
“Prior to our study, there was a theory that neurons could expand and deflate like a balloon,” said Sonal Shree, Ph.D., assistant research scientist and lead author of the study. “And we found that, no, they don’t inflate like a balloon, but they grow at the tip and branch.”
“We found that we can fully explain neuronal growth and overall morphology by what the tips of cells are doing,” said Sabyasachi Sutradhar, Ph.D., associate research scientist and co-lead author of the study.
“This means that now we can focus on the tips, because if we can understand how they work, we can understand how the whole shape of the cell is formed,” says Howard.
There is a whole world of diversity in biology, from the veins and arteries of the circulatory system to the bronchioles of the lungs. Howard’s lab hopes that a better understanding of branching at the cellular level will also shed light on these processes at the molecular and tissue levels.
This is about neurological research news
Original Research: Open access.
“The dynamic instability of dendrite tips creates highly divergent morphologies of sensory neurons.” Sonal Shree et al. Advances in science
The dynamic instability of dendrite tips creates highly divergent morphologies of sensory neurons.
Highly branched arbors of neuronal dendrites provide the substrate for the brain’s high connectivity and computational power. Altered dendritic morphology is associated with neuronal diseases.
Many molecules have been shown to play an important role in the formation and maintenance of dendrite morphology. However, the underlying principles by which molecular interactions produce branched morphologies are not understood.
To elucidate these principles, we imaged the growth of dendrites throughout larval development Drosophila found that the tips of sensory neurons and dendrites undergo dynamic instability, rapidly and stochastically switching between growing, shrinking, and suspended states.
By incorporating these measured dynamics into an agent-based computational model, we showed that the complex and highly variable dendritic morphologies of these cells result from the stochastic dynamics of their dendrite tips.
These principles may generalize to branching in other neuronal cell types, as well as to branching at the subcellular and tissue levels.