Navigation Links
St. Jude Scientists Discover a New Mechanism Controlling Neuronal Migration
Date:7/15/2009

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

MEMPHIS, Tenn., July 15 /PRNewswire-USNewswire/ -- 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. For more information, please visit www.stjude.org.


'/>"/>
SOURCE St. Jude Children's Research Hospital
Copyright©2009 PR Newswire.
All rights reserved

Related medicine news :

1. New prion protein discovered by Canadian scientists may offer insight into mad cow disease
2. Scientists Probe Sepsis Deadly Secrets
3. Scientists puzzled by severe allergic reaction to cancer drug in the middle Southern US
4. Scientists Develop Natural Protection for Stored Foods
5. Scientists detect presence of marburg virus in african fruit bats
6. Scientists Spot Brains Free Will Center
7. Scientists ID Likely Culprit in Popcorn Lung
8. Scientists explain how insulin secreting cells maintain their glucose sensitivity
9. Scripps Research scientists shed new light on how antibodies fight HIV
10. Scientists, physicians present latest findings in personalized cancer treatment and prevention
11. Scientists demonstate link between genetic variant and effectiveness of smoking cessation meds
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/25/2016)... ... June 25, 2016 , ... Austin residents seeking Mohs surgery services, ... Mohs Surgery and to Dr. Russell Peckham for medical and surgical dermatology. , Dr. ... skin cancer. The selective fellowship in Mohs Micrographic Surgery completed by Dr. Dorsey was ...
(Date:6/25/2016)... Beach, CA (PRWEB) , ... June 25, 2016 , ... ... UCLA with Magna Cum Laude and his M.D from the David Geffen School of ... Diego and returned to Los Angeles to complete his fellowship in hematology/oncology at the ...
(Date:6/24/2016)... ... June 24, 2016 , ... A recent article ... are unfamiliar with. The article goes on to state that individuals are now more ... these less common operations such as calf and cheek reduction. The Los Angeles area ...
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... ... Conference and Scientific Sessions in Dallas that it will receive two significant new ... the grants came as PHA marked its 25th anniversary by recognizing patients, medical ...
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... Topical BioMedics, Inc, makers of Topricin and ... that call for a minimum wage raise to $12 an hour by 2020 and then ... will restore the lost value of the minimum wage, assure the wage floor does not ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... -- MedSource announced today that it has selected Datatrial,s ... choice.  This latest decision demonstrates MedSource,s commitment to ... by offering a state-of-the-art electronic data capture (EDC) ... the EDC platform of choice in exchange for ... long been a preferred EDC platform by our ...
(Date:6/23/2016)... Roche (SIX: RO, ROG; OTCQX: RHHBY) announced that it ... (procalcitonin) assay as a dedicated testing solution for people ... Roche is the first IVD company in the U.S ... assessment and management. PCT is a sepsis-specific ... blood can aid clinicians in assessing the risk of ...
(Date:6/23/2016)... , , , WHEN: , , ... , , , LOCATION: , , , Online, with free registration ... PANELISTS:  , , , Frost & Sullivan,s Global Vice President of ... Analyst, Divyaa Ravishankar and Unmesh Lal, Program Manager , ... witnessing an exceptional era. Several new demand spaces, such as innovative ...
Breaking Medicine Technology: