Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Stem cell death gives clue to brain cell survival

01.08.2003


A signal that triggers half the stem cells in the developing brain to commit suicide at a stage where their survival will likely do more harm than good has been identified by researchers at the Medical College of Georgia and the University of Georgia.



Identifying the factors that result in the timely, massive cell suicide is important to understanding the developmental puzzle, the researchers say of the work featured on the cover of the Aug. 4 issue of the Journal of Cell Biology.

They say it also gives clues about cell death - and the brain´s possible recovery - in devastating diseases such as Alzheimer´s, Parkinson´s and stroke. MCG´s Erhard Bieberich and UGA´s Brian G. Condie have found that the lipid ceramide and the protein PAR-4 - each already implicated for playing a role in cell death - become deadly partners inside a dividing stem cell in the developing mouse brain.


"If PAR-4 is there and ceramide is high, the cell is lost, doomed to die," says Dr. Bieberich, biochemist at the Medical College of Georgia. "You can eliminate one of them, you can knock down the expression of PAR-4 or ceramide and the other stays up but the cell doesn´t die. But if both signals are together up-regulated, then the cell is destined to die."

At a certain point in cell division, just before neurons begin forming, there is massive production of proteins and up-regulation of lipids. During that phase, decisions are made about which daughter cells get what composition of lipids and proteins, decisions that affect the cells´ future function.

Typically at this point in division, the two daughter cells birthed from a single stem cell will have the same makeup and the same ultimate purpose.

Yet in a subpopulation of the stem cells involved in brain development, the scientists have documented increasing levels of ceramide in both resulting daughter cells while its death partner, PAR-4, gets handed off to only half the cells.

Cells destined to survive, and likely further divide and differentiate, are handed instead a protein called nestin. "Nestin is a marker for a particular stage of neuronal development," says Dr. Bieberich. "Nestin-bearing cells will develop into neural cells such as our neurons or astrocytes or other cells. So it makes sense that the cells that inherit nestin, but not PAR-4, will survive and develop into normal neuronal cells whereas the other ones will die."

It also makes sense that the lethal coupling that signals cell suicide, or apoptosis, comes at a point where the doomed cells seem to have lost their potential usefulness and where their continued survival would result in a malformed brain.

"During normal development in the central nervous system there is a great deal of cell death that occurs that seems to be required to create the final shape and structure of the brain," says Dr. Condie, developmental neurobiologist at the University of Georgia and MCG. "In cases where that process has been interfered with, you end up with this excess of cells that leads to a malformation of the developing brain.

"One of the ideas behind why there is an excess of cells generated during development is that it may be a mechanism for compensating for environmental stresses or other types of stresses that an embryo may encounter during development," says Dr. Condie. "So you actually generate an excess of the cells you need and then prune those cells back to an appropriate number and location for the brain to develop in a normal fashion." It´s a typical characteristic of embryonic development for certain cells to survive and others to die, he says.

"During embryonic development, we would like to know how stem cell death is regulated because we know it needs to be regulated," says Dr. Bieberich. "You don´t want the whole brain dying or overgrowing. You have to find a balance. How is that balanced maintained? What are the secrets for that?

"We have designed experiments showing that these two signals are necessary to make stem cells die, but you are talking about a whole signaling cascade that starts out with ceramide and PAR-4 and then there are a lot of unknown steps until we end up with the actual death of a cell," says Dr. Bieberich.

The MCG researcher recently received a grant from the National Institutes of Health so he and Dr. Condie can explore these unknowns such as how the expression of PAR-4 and ceramide is regulated, what accounts for the asymmetrical distribution of PAR-4 and just how the deadly duo interact.

But the two are excited about what they have found already. "If we don´t know the signals, we don´t know where to begin," says Dr. Bieberich.

They also are intrigued by where the work may lead, including helping minimize cell death that occurs when stem cells in the adult brain begin to once again divide in response to a stroke, as an example.

"We all know that even in adulthood, we have stem cells in the brain and they may be able to repair damaged areas," says Dr. Bieberich. "But if the same cell death mechanisms are still active, there will not be an increase in the number of stem cells because always one cell will die and one will survive. Maybe we can control this and increase the number of endogenous stem cells.

"Also during the neurodegeneration that occurs in diseases such as Alzheimer´s and Parkinson´s, we have a lot of cell death going on and we would like to know what signals are involved that make those brain cells die. They may be very similar or even exactly the same as the ones we investigate with our embryonic mouse stem cells."

Study co-authors include Scott Noggle, an MCG graduate student working with Dr. Condie at UGA; Sarah MacKinnon, a former participant in MCG´s summer research programs for undergraduates who is now a graduate student at the University of Virginia; and Dr. Jeane Silva, Dr. Bieberich´s research coordinator.

Contact: Phil Williams, (+1) 706-542-8501

Phil Williams | EurekAlert!
Further information:
http://www.uga.edu

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>