Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein Creates Paths For Growing Nerve Cells

20.12.2012
Link made between muscular dystrophy and defective nerve wiring

Working with mice, Johns Hopkins scientists have discovered that a particular protein helps nerve cells extend themselves along the spinal cord during mammalian development.


Neatly organized axons traveling up and down the spinal cord of a healthy, embryonic mouse (left). Axons in mice without dystroglycan (right) are tangled and disorganized.

Kevin Wright

Their results shed light on the subset of muscular dystrophies that result from mutations in the gene that holds the code for the protein, called dystroglycan, and also show how the nerve and muscle failings of the degenerative diseases are related.

As mammals like mice and humans develop, nerve cells in the brain and spinal cord must form connections with themselves and with muscles to assure proper control of movement. Nerve cells sometimes extend the whole length of the spinal cord to connect sensory nerves bearing information, for example, from the legs to the brain. To do so, nerve cells anchor their “headquarters,” or cell bodies, in one location, and then extend a long, thin projection all the way to their target locations. These projections, or axons, can be 10,000 times longer than the cell body.

In a report published in the journal Neuron on Dec. 6, the authors suggest that, during fetal development, axons extend themselves along specific pathways created by dystroglycan.

“Dystroglycan creates a path and then binds other molecules that act as traffic signs, providing directional cues for axons en route to their targets,” says David Ginty, Ph.D., a Howard Hughes investigator and professor of neuroscience in the Institute for Basic Biomedical Sciences at the Johns Hopkins University School of Medicine.”

To find new genes associated with axon migration, Kevin Wright, Ph.D., a postdoctoral fellow in Ginty’s laboratory, chemically provoked random genetic changes throughout the genomes of mice and then examined their axons for defective organization. What stood out were mutations in two genes that resulted in axon growth patterns similar to those in mice lacking the protein Slit, which is known to provide directional cues for nerve axons.

Digging deeper, Wright found that the mutated genes encode for the proteins B3gnt1 and ISPD, both of which had recently been implicated in adding sugar molecules to dystroglycan. Sugars bound to proteins often control their activity, so B3gnt1 and ISPD led the team to focus on dystroglycan as the key to the axon flaws they saw.

Through a series of genetic and biochemical experiments, the scientists learned that B3gnt1 and ISPD are indeed required for dystroglycan to work properly. Dystroglycan is made and released by specific cells within the spinal cord. It acts as a hub for tethering instructional molecules, like Slit, that guide nerve axons as they grow. But before dystroglycan can bind the instructional molecules, B3gnt1 and ISPD must attach sugars to it.

As expected, mice with defective dystroglycan usually have symptoms similar to mice with defective B3gnt1, ISPD or Slit. Moreover, the development of their muscles and nerves is severely disturbed, and the animals die soon after birth. Mouse fetuses completely missing any of the four proteins usually die before they are born.

Without dystroglycan or its helpers, the axons don’t know where to go and the connection between nerve cells is lost, Ginty says. “Dystroglycan creates the road, B3gnt1 and ISPD add tar on top, and directional molecules like Slit stick to the tar and point the axons in the right direction,” he explains. “If any part of the collaboration is missing, the axons overshoot their targets or don’t turn where they should.”

“Many muscular dystrophies are caused by a defect specific to muscles,” says Ginty. “Children with defects in dystroglycan suffer from muscle weakening and bad nerve connections. Now we have mice with similar symptoms that we can study further.”

Other authors of the report include Krissy Lyon and Daniel Leahy of the Johns Hopkins University School of Medicine and Haiwen Leung and Le Ma of the University of Southern California.

This work was supported by grants from the National Institute of Neurological Disorders and Stroke (NS34814, NS062047), the National Institute of Child Health and Human Development (R01HD055545), the Johns Hopkins Brain Science Institute and the Howard Hughes Medical Institute.

Media Contacts:
Catherine Kolf; 443-287-2251; ckolf@jhmi.edu
Vanessa McMains; 410-502-9410; vmcmain1@jhmi.edu
Shawna Williams; 410-955-8236; shawna@jhmi.edu

Catherine Kolf | EurekAlert!
Further information:
http://www.jhmi.edu

More articles from Life Sciences:

nachricht Scientists enlist engineered protein to battle the MERS virus
22.05.2017 | University of Toronto

nachricht Insight into enzyme's 3-D structure could cut biofuel costs
19.05.2017 | DOE/Los Alamos National Laboratory

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

Im Focus: Bacteria harness the lotus effect to protect themselves

Biofilms: Researchers find the causes of water-repelling properties

Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...

Im Focus: Hydrogen Bonds Directly Detected for the First Time

For the first time, scientists have succeeded in studying the strength of hydrogen bonds in a single molecule using an atomic force microscope. Researchers from the University of Basel’s Swiss Nanoscience Institute network have reported the results in the journal Science Advances.

Hydrogen is the most common element in the universe and is an integral part of almost all organic compounds. Molecules and sections of macromolecules are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

Innovation 4.0: Shaping a humane fourth industrial revolution

17.05.2017 | Event News

Media accreditation opens for historic year at European Health Forum Gastein

16.05.2017 | Event News

 
Latest News

New approach to revolutionize the production of molecular hydrogen

22.05.2017 | Materials Sciences

Scientists enlist engineered protein to battle the MERS virus

22.05.2017 | Life Sciences

Experts explain origins of topographic relief on Earth, Mars and Titan

22.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>