Navigation Links
Gene keeps neural cells on correct developmental path

Embryonic stem cells with identical genomes grow into distinctive tissues, such as heart, bone, and brain. At one time, scientists believed the differences among cell types arose from various sets of genes switched on inside developing cells. Then, studies showed that adult neurons uniquely lack a protein that permanently turns off neuronal genes in the rest of the body's cells.

Now, it turns out that precursor nerve cells contain that same repressive protein after all. In fact, the protein directs the complex network of genes that transforms an embryonic stem cell into a mature nerve cell, say Howard Hughes Medical Institute (HHMI) researchers.

This new study, published in the May 20, 2005, issue of the journal Cell, may be among the first to track a set of genes from stem cell to differentiated neuron. It also reveals fundamental details of how stem cells retain developmental plasticity.

"A single protein does it all," said Gail Mandel, HHMI investigator at the State University of New York at Stony Brook. "It keeps the genes totally off in non-neuronal tissues, such as skin, where you don't dare express a neuronal gene. But it also allows the full elaboration of the neuronal phenotype from the precursor cell."

Led by HHMI associate Nurit Ballas, a postdoctoral fellow in Mandel's lab, the study may advance stem cell research aimed at understanding repairing spinal cord injuries or replacing malfunctioning brain cells in neurodegenerative diseases. It may also provide insights into other diseases, such as small cell lung cancer, which mistakenly make neuronal proteins, or neurological syndromes, where neuronal proteins produced by cancers may trigger the immune cells to attack the nervous system.

The study focuses on a protein called REST, which is short for RE1-silencing transcription factor. It was independently discovered 10 years ago by Mandel's group and a second team led by HHMI investigator David J. Anderson at Caltech. Mandel created the acronym to describe how REST quiets the nerve genes. The protein is also known by the name Anderson gave it, NRSF, for neuron-restrictive silencer factor.

Since then, they and others have found that REST locks down neuronal genes in other cells by grabbing onto the DNA and cementing in other molecules, an arrangement that stays intact as non-neuronal cells differentiate into liver, muscle, and other tissues.

The new study reports that REST uses a different temporary off mechanism to direct neuronal development. "This study shows that there is more than one way to keep a REST-regulated gene repressed," said Michael G. Rosenfeld, an HHMI investigator at University of California, San Diego, who co-authored an accompanying commentary in Cell with Victoria Lunyak, a research associate in his lab.

In contrast to the tight packaging of neural genes in other cells, REST keeps the chromatin in embryonic stem and precursor neurons open and poised for gene activity.

"REST keeps the brake on lightly until a trigger tells embryonic stem cells it's time to make a neuron," Mandel said. The cell then triggers the expression of an ensemble of genes that coordinates nervous system development by removing REST in three distinct phases, ending with shutting down the REST gene.

"The cell gets rid of all the excess protein, kicks it off the DNA, then stomps on its head so it can't make RNA," Mandel said. "We can't detect REST in the terminally differentiated neuron." But some molecular partners of REST remain, perhaps fine-tuning gene expression in mature neurons, she said.

REST seems to work globally, binding to the starting points of as many as 1,000 genes at once. The gradual loss of REST in differentiating neurons probably orchestrates a precise sequence of genes sensitive to different levels of REST, Mandel speculates.

REST has been a difficult gene to study. Using knockout technology -- a popular technique f or determining gene function -- does not work for REST because mice lacking the gene die before they are born. Embryonic stem cells provided a way for Mandel to get around this problem. Unexpectedly, they also revealed fundamental ways in which stem cells remain plastic.

"This paper is like a whole story, beginning with the birth of a neuron and ending with the death of REST," Mandel said.


'"/>

Source:Howard Hughes Medical Institute


Related biology news :

1. High fidelity keeps human DNA assembly line humming
2. Life-extending protein keeps blood sugar in check
3. A resetting signal keeps circadian rhythm on track in Drosophila fruit flies
4. Unusual mechanism keeps repair protein accurate
5. Chewing up a key regulator of fat synthesis keeps mice lean despite a high-fat diet
6. Septum keeps neurons in synch, can reduce epileptic seizures by 90 percent
7. Increased sensitivity to nerve signals keeps diabetes at bay
8. A simple feedback resistor switch keeps latent HIV from awakening
9. To elude bats, a moth keeps its hearing in tune
10. Nerve cell software keeps track of brain change
11. Researchers discover stem cell guide that may be key for targeting neural stem cell treatments
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:3/16/2017)... 16, 2017 CeBIT 2017 - Against identity fraud with DERMALOG solutions ... ... Used combined in one project, multi-biometric solutions provide a crucial contribution against ... Used combined in one project, ... ...
(Date:3/9/2017)... MOUNTAIN VIEW, Calif. , March 9, 2017 ... and 23andMe , the leading personal genetics company, ... Zipongo can now provide customers with personalized nutrition plans ... and biometrics, but also genetic markers impacting how their ... Zipongo,s personalized food decision support platform uses biometrics such ...
(Date:3/6/2017)... MATEO, Calif. , March 6, 2017 /PRNewswire/ ... marketing and sales technology, today announced Predictive Sales ... solution for infusing actionable sales intelligence into Salesforce. ... to automatically enable their sales organizations with deep ... messages that allow for intelligent engagement. Predictive Sales ...
Breaking Biology News(10 mins):
(Date:3/23/2017)... ... 23, 2017 , ... Ellen Matloff, president and CEO of ... as a 2017 Women of Innovation® finalist. Matloff will be among several women ... The dinner recognizes women accomplished in science, technology, engineering and math (STEM), along ...
(Date:3/23/2017)... , March 23, 2017 NetworkNewsWire ... ... death, putting significant strain on health care systems, in terms ... diagnoses rises, so too does the development of innovative and ... side effects. Among the many types of cancer treatments, a ...
(Date:3/23/2017)... , March 23, 2017  Agriculture technology company ... A financing and note conversion to commercialize its Cool ... is focused on developing products that are simultaneously profitable ... million in the last 18 months. This latest round ... Bridge Venture Partners. The company,s primary ...
(Date:3/23/2017)... New Orleans, La. (PRWEB) , ... March 23, ... ... of real-time, industrial monitoring solutions, today announced the hire of Dr. Sigmund “Sig” ... for APMT customer applications, strategic partnerships and joint development activities. , “Dr. Floyd’s ...
Breaking Biology Technology: