Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Lack of Protein Sp2 Disrupts Neuron Creation in Brain

16.01.2013
A protein known as Sp2 is key to the proper creation of neurons from stem cells, according to researchers at North Carolina State University. Understanding how this protein works could enable scientists to “program” stem cells for regeneration, which has implications for neural therapies.

Troy Ghashghaei and Jon Horowitz, both faculty in NC State’s Department of Molecular Biomedical Sciences and researchers in the Center for Comparative Medicine and Translational Research, wanted to know more about the function of Sp2, a cell cycle regulator that helps control how cells divide.


NC State University

A rendered image of a primary neuronal stem cell culture in which cells were labeled with different fluorescently labeled proteins that differentiate between stem cells (orange/yellow) and their neuronal 'offspring' (blue/green/purple). Neural stem cells are dependent on a protein called Sp2 for their ability to generate neurons.

Previous research from Horowitz had shown that too much Sp2 in skin-producing stem cells resulted in tumors in experimental mice. Excessive amounts of Sp2 prevented the stem cells from creating normal cell “offspring,” or skin cells. Instead, the stem cells just kept producing more stem cells, which led to tumor formation.

“We believe that Sp2 must play a fundamental role in the lives of normal stem cells,” Horowitz says. “Trouble ensues when the mechanisms that regulate its activity are overwhelmed due to its excess abundance.”

Ghashghaei and his team – led by doctoral candidate Huixuan Liang – took the opposite approach. Using genetic tools, they got rid of Sp2 in certain neural stem cells in mice, specifically those that produce the major neurons of the brain’s cerebral cortex. They found that a lack of Sp2 disrupted normal cell formation in these stem cells, and one important result was similar to Horowitz’s: the abnormal stem cells were unable to produce normal cell “offspring,” or neurons. Instead, the abnormal stem cells just created copies of themselves, which were also abnormal.

“It’s interesting that both an overabundance of this protein and a total lack of it result in similar disruptions in how stem cells divide,” Ghashghaei says. “So while this work confirms that Sp2 is absolutely necessary for stem cell function, a lot of questions still remain about what exactly it is regulating, and whether it is present in all stem cells or just a few. We also need to find out if Sp2 deletion or overabundance can produce brain tumors in our mice as in the skin.

“Finally, we are very interested in understanding how Sp2 regulates a very important decision a stem cell has to make: whether to produce more of itself or to produce offspring that can become neurons or skin cells,” Ghashghaei adds. “We hope to address those questions in our future research, because these cellular mechanisms have implications for cancer research, neurodevelopmental diseases and regenerative medicine.”

The results appear online in Development. NC State graduate students Guanxi Xiao, and Haifeng Yin, as well as Dr. Simon Hippenmeyer, a collaborator with the Ghashghaei lab from Austria’s Institute of Science and Technology, contributed to the work. The work was funded by the National Institutes of Health and the American Federation for Aging Research.

Note to editors: Abstract follows

“Neural development is dependent on the function of specificity protein 2 in cell cycle progression”

Authors: Huixuan Liang, Guanxi Xiao, Haifeng Yin, Jonathan M. Horowitz and H. Troy Ghashghaei, NC State University; Simon Hippenmeyer, Institute of Science and Technology, Klosterneuburg, Austria

Published: Development

Abstract:
Faithful progression through the cell cycle is crucial to the maintenance and developmental potential of stem cells. Here, we demonstrate that neural stem cells (NSCs) and intermediate neural progenitor cells (NPCs) employ a zinc-finger transcription factor specificity protein 2 (Sp2) as a cell cycle regulator in two temporally and spatially distinct progenitor domains. Differential conditional deletion of Sp2 in early embryonic cerebral cortical progenitors, and perinatal olfactory bulb progenitors disrupted transitions through G1, G2 and M phases, whereas DNA synthesis appeared intact. Cell-autonomous function of Sp2 was identified by deletion of Sp2 using mosaic analysis with double markers, which clearly established that conditional Sp2-null NSCs and NPCs are M phase arrested in vivo. Importantly, conditional deletion of Sp2 led to a decline in the generation of NPCs and neurons in the developing and postnatal brains. Our findings implicate Sp2-dependent mechanisms as novel regulators of cell cycle progression, the absence of which disrupts neurogenesis in the embryonic and postnatal brain.

Tracey Peake | Newswise
Further information:
http://www.ncsu.edu

More articles from Life Sciences:

nachricht Fruit fly studies shed light on adaptability of nerve cells
17.04.2015 | Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE)

nachricht Rare monkey photographed in Congo's newest national park, Ntokou-Pikounda
17.04.2015 | Wildlife Conservation Society

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Astronomers reveal supermassive black hole's intense magnetic field

Astronomers from Chalmers University of Technology have used the giant telescope Alma to reveal an extremely powerful magnetic field very close to a supermassive black hole in a distant galaxy

Astronomers from Chalmers University of Technology have used the giant telescope Alma to reveal an extremely powerful magnetic field very close to a...

Im Focus: A “pin ball machine” for atoms and photons

A team of physicists from MPQ, Caltech, and ICFO proposes the combination of nano-photonics with ultracold atoms for simulating quantum many-body systems and creating new states of matter.

Ultracold atoms in the so-called optical lattices, that are generated by crosswise superposition of laser beams, have been proven to be one of the most...

Im Focus: UV light robot to clean hospital rooms could help stop spread of 'superbugs'

Can a robot clean a hospital room just as well as a person?

According to new research out of the Texas A&M Health Science Center College of Medicine, that is indeed the case. Chetan Jinadatha, M.D., M.P.H., assistant...

Im Focus: Graphene pushes the speed limit of light-to-electricity conversion

Researchers from ICFO, MIT and UC Riverside have been able to develop a graphene-based photodetector capable of converting absorbed light into an electrical voltage at ultrafast timescales

The efficient conversion of light into electricity plays a crucial role in many technologies, ranging from cameras to solar cells.

Im Focus: Study shows novel pattern of electrical charge movement through DNA

Electrical charges not only move through wires, they also travel along lengths of DNA, the molecule of life. The property is known as charge transport.

In a new study appearing in the journal Nature Chemistry, authors, Limin Xiang, Julio Palma, Christopher Bruot and others at Arizona State University's...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

HHL's Entrepreneurship Conference on FinTech

13.04.2015 | Event News

World Conference On Regenerative Medicine 2015: Registration And Abstract Submission Now Open

25.03.2015 | Event News

University presidents from all over the world meet in Hamburg

19.03.2015 | Event News

 
Latest News

Engineer Improves Rechargeable Batteries with MoS2 Nano 'Sandwich'

17.04.2015 | Power and Electrical Engineering

Comparing Climate Models to Real World Shows Differences in Precipitation Intensity

17.04.2015 | Earth Sciences

A blueprint for clearing the skies of space debris

17.04.2015 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>