Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

St. Jude scientists discover a new mechanism controlling neuronal migration

20.07.2009
Understanding how neurons migrate to their proper place during brain development will offer insights into how malfunctions in the machinery cause epilepsy and mental retardation

The molecular machinery that helps brain cells migrate to their correct place in the developing brain has been identified by scientists at St. Jude Children's Research Hospital.

The finding offers new insight into the forces that drive brain organization in developing fetuses and children during their first years. Disruption of this brain-patterning machinery can cause epilepsy and mental retardation and understanding its function could give new insight into such disorders.

Led by David Solecki, Ph.D., an assistant member in the St. Jude Department of Developmental Neurobiology, the researchers published their findings in the July 16 issue of the journal Neuron.

In the experiments, the researchers sought to understand the biological machinery powering a process called glial-guided neuronal migration. Glial cells in the brain support and guide neurons, which make up the brain's wiring. During brain development, neurons are born in germinal zones at some distance from where they must ultimately land in order to form brain structures and integrate into the brain's circuitry.

"Glial cells produce very thin fibers, and neurons in essence walk a tightrope along these fibers in moving from these germinal zones to their final position," Solecki said. In earlier work, Solecki and his colleagues identified a control molecule called Par6 alpha that regulates this migration. Other researchers had produced evidence that a molecular motor called Myosin II might power the migration. Myosins are proteins that use chemical energy to create contractions by moving along filamental proteins called actins—like a train moves along a railroad track.

The researchers used a technique of microscopic time-lapse imaging to establish that Myosin II and actin made up the machinery of neuronal migration. Working with cultures of migrating neurons, the investigators used fluorescent dyes to label Myosin II and actin proteins, as well as key cell structures. The scientists then illuminated the cultures with rapid-fire pulses of laser light measured in thousandths of a second, taking an image with each flash. The result was a series of micromovies that revealed how the Myosin II and actin proteins and cell structures behaved during migration.

These micromovies showed that the Myosin II-actin machinery powers neuronal migration. As part of a step-wise migration process, the machinery pulls the internal cell structures of the neuron forward during migration to allow those structures to build the scaffolding that enables the neuron to move the main cell body forward. The researchers demonstrated that both Myosin II and actin are necessary for the process, because they could completely shut it down by using drugs that inhibited either molecule.

"No one had actually looked in living cells to see the configuration of actin in migrating neurons to show how it positions the machinery that will eventually elicit movement of the cell," Solecki said. "We also found that contraction of Myosin II in the leading portion of a neuron powers movement."

Critical to the researchers' success was the development of a computer analysis technique for the massive number of time-lapse images, Solecki said. The analysis program was developed by study co-authors Ryan Kerekes, Ph.D., and Shaun Gleason, Ph.D., of Oak Ridge National Laboratories in Tennessee.

"Our time-lapse microscopy could image hundreds of cells in a single afternoon, but analyzing that mass of data by hand would have taken months," Solecki said. "However, the automated analysis enabled those data to be analyzed in a matter of hours. Also, the automated analysis was free of the kind of natural bias that can occur when humans analyze such images."

In further experiments, the researchers also showed that Par6 alpha regulates Myosin II motor activity, shedding light on how the machinery is regulated. Additional studies will explore that regulation mechanism further.

Basic understanding of the migration machinery could have important clinical implications.

"If we more clearly understand how neurons migrate in neural development, we will have a better framework to explain the basis of neuronal migration defects in children," Solecki said. "Also, cell migrations may contribute towards the spread of brain tumors in children. If we can understand how normal neurons migrate, we might be able to dissect the machinery of the migration of brain tumor cells."

Other authors of the paper are Niraj Trivedi (St. Jude); and Eve-Ellen Govek and Mary Hatten (The Rockefeller University, New York). The research was supported in part by the March of Dimes, the National Institutes of Health, a Cancer Center Support Grant and ALSAC.

St. Jude Children's Research Hospital

St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fundraising organization.

Summer Freeman | EurekAlert!
Further information:
http://www.stjude.org

More articles from Life Sciences:

nachricht BigH1 -- The key histone for male fertility
14.12.2017 | Institute for Research in Biomedicine (IRB Barcelona)

nachricht Guardians of the Gate
14.12.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Plasmonic biosensors enable development of new easy-to-use health tests

14.12.2017 | Health and Medicine

New type of smart windows use liquid to switch from clear to reflective

14.12.2017 | Physics and Astronomy

BigH1 -- The key histone for male fertility

14.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>