Both the rate and direction of axon growth in the spinal cord can be controlled, according to new research by USC College's Samantha Butler and her collaborators.
The study, "The Bone Morphogenetic Protein Roof Plate Chemorepellent Regulates the Rate of Commissural Axonal Growth," by Butler; lead researcher Keith Phan and graduate students Virginia Hazen and Michele Frendo of USC College; and Zhengping Jia of the University of Toronto, was published online in the November 17 issue of the Journal of Neuroscience.
Butler, assistant professor of biological sciences, found that a series of connections at the cellular level produce a guidance cue that tells an axon how fast and in which direction to grow in an embryonic environment. Butler and her team also discovered that by modulating the activity of enzyme LIM domain kinase 1 (Limk1), the rate of axon growth can be stalled or accelerated.
Future applications of these findings may include enhancing the ability to regenerate neuronal circuits in patients suffering from spinal cord injuries or neurodegenerative diseases.
Initially, to understand these guidance cues, Butler and her colleagues studied the mechanisms by which neuronal circuits first develop in the embryonic states of rodents and chickens. While researching how an axon is programmed to grow in a particular direction, Butler and her group made a surprising discovery.
"We were expecting that when we perturbed the signaling pathway, the axon would be confused in terms of direction," Butler said. "But we found a much greater effect — the axon grew at a different speed."
Under normal conditions, guidance cues cause a developing neuron to extend an axon into the environment. In a developing spinal cord, the cue comes in the form of a repellant, which acts from behind the cell body to direct the growth of the axon in the opposite direction. This repellant is mediated by bone morphogenetic proteins (BMPs).
In the beginning of the multi-step growth process, BMPs bind to a cell and activate its receptors; then a second messenger is triggered, in this case Limk1. Limk1 modifies the activity of a protein called cofilin. When cofilin is active, the axon grows. If the cofilin becomes inactive, growth comes to a halt.
Butler and her team discovered that by increasing the amount of cofilin, or decreasing the amount of the restricting Limk1, the commissural axon growth accelerated. Likewise, when the amount of cofilin was decreased, or the amount of Limk1 was increased, axon growth stopped.
The axon growth in embryonic spinal cords in which Limk1 was lowered appeared to be more advanced than in controls — the axons grew up to 25 percent faster.
Since the axon is growing through an ever-changing environment, if the accelerated rate moves the axon to its subsequent signal destination too fast, that destination may not yet be created. As a result, growth acceleration can lead to errors in the process, Butler said. She hopes to determine the optimal rate of acceleration that prevents these errors but still supports enhanced regeneration.
"That the growth of axons needs to be controlled in time as well as space is something that is an interesting piece of biology," Butler said. "How it can be applied is very exciting."
Butler sees the application of this research as one part of the process for rebuilding damaged circuits in patients who have sustained spinal cord injuries, or those suffering from Parkinson's or Alzheimer's diseases, possibly using stem-cell-derived therapy. The average rate of axon growth is just 1 mm per day, so any increase would improve a patient's treatment.
"If we knew how to modulate cofilin to maximize the speed of axon growth," Butler said, "perhaps we could shave time off that process of circuit regeneration."
Read the full text of the article at http://www.jneurosci.org/cgi/content/full/30/46/15430
Laurie Moore | EurekAlert!
Penn studies find promise for innovations in liquid biopsies
30.03.2017 | University of Pennsylvania School of Medicine
'On-off switch' brings researchers a step closer to potential HIV vaccine
30.03.2017 | University of Nebraska-Lincoln
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
30.03.2017 | Health and Medicine
30.03.2017 | Health and Medicine
30.03.2017 | Medical Engineering