UNC-TV Science: March 6, 2014
Fruit Fly Proteins Can Reshape Their Nervous Systems, Maybe Ours as Well
Let’s start with a thought experiment. You can manipulate your hand because your nervous system connects your brain to the muscles in your hand and wrist. You can move one finger at a time because there is a specific neuron or group of neurons that control that single finger.
Here’s the experiment. Would the nerves in your hand look the same if you had seven fingers instead of five? How about if your fingers were shortened by a knuckle? What if you had feet where your hands should be?
The short answer is yes. As humans, we develop most of our nervous system before we’re born, and from there, the broadest strokes of our neuroanatomy are pretty much set.
But picture an organism like the fruit fly, which undergoes a huge physiological change in its transition from a larva into an adult fly. It makes sense that a fruit fly would need a wildly different arrangement of its neurons as an adult fly with complex legs, wings and other organs than it would as a blob-shaped larva. But given the complexity of even a fruit fly’s nervous system, such a large transition must be an incredibly difficult process, leading scientists to question how it works.
This question interested Duke University neurobiologist Dr. Chay Kuo because humans largely lack the ability to rebuild their neurons after serious brain injuries. If a fruit fly can completely tear down and rebuild its nervous system, the thinking goes, maybe humans can borrow that technique to repair damaged neurons. So Kuo led a study to figure out exactly what fruit fly larvae do to their nervous systems when the time comes to transform into adult flies.
Neurons receive signals through a series of branched connectors called dendrites. They need to be placed precisely so that the electrical and chemical signals they get from other cells reach the rest of the neuron and get passed along. Kuo found that in many fruit fly neurons, the dendrites are completely removed during the transformation from larva to adult. Imagine lopping all the branches off a tree. More importantly the dendrites grow back in a completely different shape than they started in, completely restructuring the nervous system.
One of the major problems in human brain injuries is that dendrites get moved and damaged around so they can’t properly receive signals, so Kuo wanted to find out how the fruit fly neurons know exactly where and when to build their new dendrites. And to answer this question, the team of researchers actually got some help from mammal neurons.
The group discovered that the key protein involved in dendrite regrowth in flies is an enzyme called Cysteine proteinase-1 (Cp1), and without Cp1, dendrites don’t grow. It turns out that Cp1 has a cousin in mammals, called lysosomal protein capthesin-L (Ctsl). In a completely unrelated study, researchers discovered that Ctsl has the ability to travel into a neuron’s nucleus and track down what’s called a transcription factor, a protein that binds to a specific section of DNA to control how that DNA gets expressed. Cstl cuts that transcription factor, changing how the transcription factor attaches to DNA.
Kuo, decided to see whether Cp1 did the same thing, so he monitored Cp1 and the transcription factor, Cut, during fruit fly metamorphosis. He found that Cp1 did indeed enter the nucleus and change Cut’s binding pattern. In the larval stage, Cut bound DNA in large blobs, but in the adult stage, it spread out to different DNA strands, thus reprogramming the DNA to make adult dendrites.
While this research is a long way from having any immediate human application, it does provide a possible avenue for repairing brain injuries. As human Ctsl perfoms the same function as Cp1 does in flies, further research may reveal a method by which Ctsl can be influenced to reprogram human transcription factors into a “repair” mode.
Kuo’s work appeared in the journal Cell Reports.
- Daniel Lane
Daniel Lane covers science, medicine and the environment as a reporter/writer. He is currently pursuing a master's degree in medical and science journalism at UNC Chapel Hill.