Glial cells, not neurons, lead the way in brain assembly

December 6, 2017
Glial cells, not neurons, lead the way in brain assembly
Brain formation in worms goes awry when glial cell signaling is disrupted (right). Credit: Rockefeller University

As the very first neurons come together to form the brain, they need pointers to end up in the right places. Where do these directions come from?

Rockefeller scientists have discovered that they originate from an unlikely source, revealing that the cells directing the very first steps of assembly are not other neurons, as scientists have long assumed, but so-called .

"While glial cells are abundant in the brain, their functions are much less understood," says Shai Shaham, Richard E. Salomon Family Professor. "We've shown that in the roundworm C. elegans, glial cells play a pivotal role, coaxing neurons onto a specific path so that proper brain assembly can ensue."

Shaham and his team also found that these worm glial cells are remarkably similar to their vertebrate counterparts.

To peek inside the earliest stages of brain development, scientists must observe and analyze embryos, which are notoriously tricky to study. But research associate Georgia Rapti, the lead author of a recent Nature Neuroscience report describing this work, was able to use C. elegans as a model to tease apart how brain assembly begins.

"We found that glial cells grow radial processes, or extensions, marking where the first axons must go, and they release multiple signals to guide neurons onto the correct path," says Rapti. "Our experiments show that when glial cells or their signals are compromised, the worm's brain is severely disrupted—more than 60 percent of its neuronal extensions fail to enter the brain as they normally would."

Rapti and Shaham were also able to show that once glial cells have set the stage for brain assembly, a special group of 10 neurons, called pioneer neurons, are the first to follow suit. Pioneer neurons had previously been documented in other species, but their identities, molecular functions, and growth properties were generally unknown.

The researchers discovered a molecular signature for pioneer neurons, and showed that these cells can act with glial cells to recruit follower neurons. They were also able to uncover previously hidden molecular pathways that glial cells and pioneer neurons use to attract the next set of neurons into the brain.

While C. elegans may not seem to have a lot in common with humans and other vertebrates, their brain assembly processes resemble ours at the molecular level. For example, Rapti and Shaham note recent reports revealing that the assembly of the mouse spinal cord relies on a signaling molecule called Netrin, which is produced by radial glial cells. The researchers found that Netrin functions similarly in the worm—glial cells produce this molecule, which guides pioneer  to form the C. elegans brain.

"The glial cells driving brain assembly in the worm look like—and function similarly to—those in the vertebrate spinal cord," says Shaham. "We think of glial as the Pied Piper for nervous system assembly across animals, and the Piper's pipe appears to be the same from worms to mammals."

Explore further: CD38 gene is identified to be important in postnatal development of the cerebral cortex

More information: Georgia Rapti et al. Glia initiate brain assembly through noncanonical Chimaerin–Furin axon guidance in C. elegans, Nature Neuroscience (2017). DOI: 10.1038/nn.4630

Related Stories

CD38 gene is identified to be important in postnatal development of the cerebral cortex

April 7, 2017
The brain consists of neurons and glial cells. The developmental abnormality of glial cells causes various diseases and aberrant cerebral cortex development. CD38 gene knockout is shown to cause aberrant development of glial ...

A common brain cell shapes the nervous system in unexpected ways

April 11, 2016
More than half of our brains are made up of glial cells, which wrap around nerve fibers and insulate them—similarly to how the plastic casing of an electric cable insulates the copper wire within—allowing electrical and ...

Researchers develop new animal model to study rare brain disease

March 17, 2017
Thanatophoric dysplasia (TD) is an intractable disease causing abnormalities of bones and the brain. In a recent study of ferrets, which have brains similar to those of humans, researchers using a newly developed technique ...

Conversion of brain cells offers hope for Parkinson's patients

April 11, 2017
Researchers at Karolinska Institutet have made significant progress in the search for new treatments for Parkinson's disease. By manipulating the gene expression of non-neuronal cells in the brain, they were able to produce ...

OHSU discovery may someday lead to prevention and treatment of sudden infant death syndrome

February 16, 2012
Researchers at Oregon Health & Science University have discovered that brain cells commonly thought to play a supporting role actually are critically important for the growth of brainstem neurons responsible for cardiorespiratory ...

Recommended for you

Gene mutation causes low sensitivity to pain

December 13, 2017
A UCL-led research team has identified a rare mutation that causes one family to have unusually low sensitivity to pain.

Activating MSc glutamatergic neurons found to cause mice to eat less

December 13, 2017
(Medical Xpress)—A trio of researchers working at the State University of New York has found that artificially stimulating neurons that exist in the medial septal complex in mouse brains caused test mice to eat less. In ...

Scientists discover blood sample detection method for multiple sclerosis

December 13, 2017
A method for quickly detecting signs of multiple sclerosis has been developed by a University of Huddersfield research team.

LLNL-developed microelectrodes enable automated sorting of neural signals

December 13, 2017
Thin-film microelectrode arrays produced at Lawrence Livermore National Laboratory (LLNL) have enabled development of an automated system to sort brain activity by individual neurons, a technology that could open the door ...

Intermittent fasting found to increase cognitive functions in mice

December 12, 2017
(Medical Xpress)—The Daily Mail spoke with the leader of a team of researchers with the National Institute on Aging in the U.S. and reports that they have found that putting mice on a diet consisting of eating nothing every ...

Discovery deepens understanding of brain's sensory circuitry

December 12, 2017
Because they provide an exemplary physiological model of how the mammalian brain receives sensory information, neural structures called "mouse whisker barrels" have been the subject of study by neuroscientists around the ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

Spaced out Engineer
not rated yet Dec 06, 2017
I thought mitochondria lead the neural tubes to their place in fetus brains, but the idea was to cram as much pizza as you can in there, hence the convolutions.

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.