The dynamics of directed axon migration in the brain

February 28, 2018, Nara Institute of Science and Technology
Mutation in CRASH syndrome leads to dysfunction of the grip & slip mechanism and disrupts laminin-induced axonal haptotaxis. Credit: Naoyuki Inagaki

In a new study, NAIST scientists, in collaboration with researchers at the Osaka National Hospital and University of Tokyo, report that the L1 Cell Adhesion Molecule (L1-CAM) is crucial for directed axon migration. The study shows that L1-CAM grips and slips on laminin to steer axons to their final destination. It further explains how disruption of this L1-CAM system leads to CRASH syndrome, which describes an assortment of neural disabilities that are all attributed to an underdeveloped brain. The study is published in the Proceedings of the National Academy of Sciences (PNAS).

Axons sprout from neurons and migrate to specific parts of the developing brain where they interact with other neurons to form neural networks. The axons move in response to gradients of attractants with extraordinary sensitivity; the sudden stops and sharp turns they make during their migration resemble cars stopping and turning at an intersection.

"Laminins function as attractive chemical cues for haptotaxis of axonal growth cones," explains NAIST Prof. Naoyuki Inagaki, whose lab studies how forces are generated in the cellular microenvironment to create directed axonal migration.

Axons migrate in response to laminin on the microenvironment. The new study by the Inagaki lab showed that neurons will produce four times more traction force when placed on adhesive substrates coated with laminin than those without laminin, assuring the axons reach their final destination.

"The force reduced the F-actin retrograde flow," said Kouki Abe, a doctoral student in the lab who conducted the experiments. "We looked at the movement of L1-CAM because it is linked to F1-actin flow."

Actin is a crucial molecule for cell motility throughout the body. However, in axons, it does not directly interact with laminin. Rather, L1-CAM acts as the intermediary. As expected, additional experiments by Abe showed that the F1-actin flow was dependent on L1-CAM interactions with laminin.

"We found L1-CAM switches between an immobilized state, or what we call 'grip' state, and a 'slip' state. The ratio of grip state increased with laminin," said Inagaki. This increased grip state strengthens the traction force produced by the axon onto the adhesive substrate, allowing the axon to turn and change its direction on cue. The scientists further found that disrupting the increased grip ratio compromised the directional migration, a discovery that could explain the pathogenesis of several diseases.

"We examined L1-CAM from a patient with CRASH syndrome in which L1-CAM was mutated. The different grip ratio seen between laminin and polylysine was lost, and the directional axon migration was disturbed (Figure)", said Inagaki.

"L1-CAM controls not only in the brain, but also in cancer. Grip-and-slip is a new mechanism that could explain other diseases," he said.

Explore further: A single protein activates the machinery needed for axon growth and holds the axons together for collective extension

More information: Kouki Abe et al, Grip and slip of L1-CAM on adhesive substrates direct growth cone haptotaxis, Proceedings of the National Academy of Sciences (2018). DOI: 10.1073/pnas.1711667115

Related Stories

A single protein activates the machinery needed for axon growth and holds the axons together for collective extension

November 21, 2014
During brain development, neurons extend projections called axons to connect with other neurons. Axons from groups of neurons with the same function tend to extend together, but the mechanisms involved in keeping the growing ...

'Simple, but powerful' model reveals mechanisms behind neuron development

December 18, 2017
All things must come to an end. This is particularly true for neurons, especially the extensions called axons that transmit electrochemical signals to other nerve cells. Without controlled termination of individual neuron ...

New microdevice prepares axon fascicles in the lab like those seen in the brain

October 26, 2017
Axons are the structures through which neurons transmit information to other cells. In the body, they aggregate to form fascicles. Several technologies allow scientists to generate and study single axons in the lab, but none ...

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 ...

Recommended for you

Newborn babies' brain responses to being touched on the face measured for the first time

November 16, 2018
A newborn baby's brain responds to being touched on the face, according to new research co-led by UCL.

Precision neuroengineering enables reproduction of complex brain-like functions in vitro

November 14, 2018
One of the most important and surprising traits of the brain is its ability to dynamically reconfigure the connections to process and respond properly to stimuli. Researchers from Tohoku University (Sendai, Japan) and the ...

New brain imaging research shows that when we expect something to hurt it does, even if the stimulus isn't so painful

November 14, 2018
Expect a shot to hurt and it probably will, even if the needle poke isn't really so painful. Brace for a second shot and you'll likely flinch again, even though—second time around—you should know better.

A 15-minute scan could help diagnose brain damage in newborns

November 14, 2018
A 15-minute scan could help diagnose brain damage in babies up to two years earlier than current methods.

New clues to the origin and progression of multiple sclerosis

November 13, 2018
Mapping of a certain group of cells, known as oligodendrocytes, in the central nervous system of a mouse model of multiple sclerosis (MS), shows that they might have a significant role in the development of the disease. The ...

Mutations, CRISPR, and the biology behind movement disorders

November 12, 2018
Scientists at the RIKEN Center for Brain Science (CBS) in Japan have discovered how mutations related to a group of movement disorders produce their effects. Published in Proceedings of the National Academy of Sciences, the ...

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.