Study overturns seminal research about the developing nervous system

April 20, 2017 by Mirabai Vogt-James
Left: axons (green, pink, blue) form organized patterns in the normal developing mouse spinal cord. Right: removing netrin1 results in highly disorganized axon growth. Credit: UCLA Broad Stem Cell Research Center/Neuron

New research by scientists at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA overturns a long-standing paradigm about how axons—thread-like projections that connect cells in the nervous system—grow during embryonic development. The findings of the study, led by Samantha Butler, associate professor of neurobiology, could help scientists replicate or control the way axons grow, which may be applicable for diseases that affect the nervous system, such as diabetes, as well as injuries that sever nerves.

As an embryo grows, neurons—the cells in the nervous —extend axons into the developing spinal cord. Axons are then guided to reach other areas of the body, such as the brain, to establish a functioning nervous system. It has been generally understood that various guidance cues, which are cellular molecules such as proteins, either attract or repel as the axons reach out from neurons to find their destination in the nervous system.

Previous research suggested that a particular guidance cue, called netrin1, functions over a long distance to attract and organize axon growth, similar to how a lighthouse sends out a signal to orient a ship from afar. However, previous research also shows that netrin1 is produced in many places in the embryonic , raising questions about whether it really acts over a long distance. Most notably, netrin1 is produced by tissue-specific stem cells, called neural progenitors, which can create any cell type in the nervous system. Yet, it was not understood how the netrin1 produced by neural progenitors influences axon growth.

Butler and her research team removed netrin1 from neural progenitors in different areas in mouse embryonic spinal cords. This manipulation resulted in highly disorganized and abnormal axon growth, giving the researchers a very detailed view of how netrin1 produced by neural progenitors influences axons in the developing nervous system.

They found that neural progenitors organize axon growth by producing a pathway of netrin1 that directs axons only in their local environment and not over long distances. This pathway of netrin1 acts as a sticky surface that encourages axon growth in the directions that form a normal, functioning nervous system.

Butler's study is a significant reinterpretation of the role of netrin1 in nervous system formation. The results further scientists' understanding of the contribution neural progenitors make to neural circuit formation. Determining how netrin1 specifically influences axon could help scientists use netrin1 to regenerate axons more effectively in patients whose nerves have been damaged.

For example, because nerves grow in channels, there is much interest in trying to restore channels after an injury that results in severed nerves, which is seen often in patients who have experienced an accident or in veterans with injuries to their arms or legs. One promising approach is to implant artificial nerve channels into a person with a nerve injury to give regenerating axons a conduit to grow through. Butler believes that coating such nerve channels with netrin1 could further encourage axon regrowth. Her continued research will focus on uncovering more details about how netrin1 functions and how it could be used clinically.

The study is published today in the journal Neuron.

Explore further: Cell biologists discover crucial 'traffic regulator' in neurons

More information: Neuron (2017). www.cell.com/pb-assets/journal … w/neuron13632_r2.pdf

Related Stories

Cell biologists discover crucial 'traffic regulator' in neurons

April 19, 2017
Cell biologists from Utrecht University have discovered the protein that may be the crucial traffic regulator for the transport of vital molecules inside nerve cells. When this traffic regulator is removed, the flow of traffic ...

Researchers discover how neurons tell each other to die under trauma, disease

March 9, 2017
A major contributor to most neurological diseases is the degeneration of a wire-like part of nerve cells called an axon, which electrically transmits information from one neuron to another. The molecular programs underlying ...

Molecule shown to repair damaged axons

March 8, 2017
A foray into plant biology led one researcher to discover that a natural molecule can repair axons, the thread-like projections that carry electrical signals between cells. Axonal damage is the major culprit underlying disability ...

Connection discovered between the nervous system and the vascular system

June 8, 2011
Dr. Frédéric Charron, researcher at the Institut de recherches cliniques de Montréal (IRCM), and his team have shown for the first time that a key molecule of the vascular system directs axons during the formation ...

Researchers uncover a new piece of the puzzle in the development of our nervous system

July 14, 2011
Researchers at the Institut de recherches cliniques de Montréal (IRCM) are among the many scientists around the world trying to unearth our nervous system's countless mysteries. Dr. Artur Kania, Director of the IRCM's ...

Recommended for you

'Selfish brain' wins out when competing with muscle power, study finds

October 20, 2017
Human brains are expensive - metabolically speaking. It takes lot of energy to run our sophisticated grey matter, and that comes at an evolutionary cost.

Researchers find shifting relationship between flexibility, modularity in the brain

October 19, 2017
A new study by Rice University researchers takes a step toward what they see as key to the advance of neuroscience: a better understanding of the relationship between the brain's flexibility and its modularity.

Want to control your dreams? Here's how

October 19, 2017
New research at the University of Adelaide has found that a specific combination of techniques will increase people's chances of having lucid dreams, in which the dreamer is aware they're dreaming while it's still happening ...

Brain training can improve our understanding of speech in noisy places

October 19, 2017
For many people with hearing challenges, trying to follow a conversation in a crowded restaurant or other noisy venue is a major struggle, even with hearing aids. Now researchers reporting in Current Biology on October 19th ...

Investigating the most common genetic contributor to Parkinson's disease

October 19, 2017
LRRK2 gene mutations are the most common genetic cause of Parkinson's disease (PD), but the normal physiological role of this gene in the brain remains unclear. In a paper published in Neuron, Brigham and Women's Hospital ...

Brain takes seconds to switch modes during tasks

October 19, 2017
The brain rapidly switches between operational modes in response to tasks and what is replayed can predict how well a task will be completed, according to a new UCL study in rats.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.