Lack of protein Sp2 disrupts neuron creation in brain

January 14, 2013, North Carolina State University
Lack of protein Sp2 disrupts neuron creation in brain
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).

(Medical Xpress)—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 and Translational Research, wanted to know more about the function of Sp2, a cell cycle regulator that helps control how cells divide. 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 .

"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 Huixuan Liang – took the opposite approach. Using , they got rid of Sp2 in certain in mice, specifically those that produce the major neurons of the brain's . They found that a lack of Sp2 disrupted normal 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 ," 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.

Explore further: Genetic 'conductor' involved with new brain cell production in adults

More information: "Neural development is dependent on the function of specificity protein 2 in cell cycle progression" Development, 2013.

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.

Related Stories

Genetic 'conductor' involved with new brain cell production in adults

June 29, 2011
A team of North Carolina State University researchers has discovered more about how a gene connected to the production of new brain cells in adults does its job. Their findings could pave the way to new therapies for brain ...

New role for Vascular Endothelial Growth Factor in regulating skin cancer stem cells

October 19, 2011
Skin squamous cell carcinomas are amongst the most frequent cancers in humans. Recent studies suggest that skin squamous cell carcinoma, like many other human cancers, contain particular cancer cells, known as cancer stem ...

Recommended for you

New neuron-like cells allow investigation into synthesis of vital cellular components

January 22, 2018
Neuron-like cells created from a readily available cell line have allowed researchers to investigate how the human brain makes a metabolic building block essential for the survival of all living organisms. A team led by researchers ...

Finding unravels nature of cognitive inflexibility in fragile X syndrome

January 22, 2018
Mice with the genetic defect that causes fragile X syndrome (FXS) learn and remember normally, but show an inability to learn new information that contradicts what they initially learned, shows a new study by a team of neuroscientists. ...

Epilepsy linked to brain volume and thickness differences

January 22, 2018
Epilepsy is associated with thickness and volume differences in the grey matter of several brain regions, according to new research led by UCL and the Keck School of Medicine of USC.

Research reveals atomic-level changes in ALS-linked protein

January 18, 2018
For the first time, researchers have described atom-by-atom changes in a family of proteins linked to amyotrophic lateral sclerosis (ALS), a group of brain disorders known as frontotemporal dementia and degenerative diseases ...

Fragile X finding shows normal neurons that interact poorly

January 18, 2018
Neurons in mice afflicted with the genetic defect that causes Fragile X syndrome (FXS) appear similar to those in healthy mice, but these neurons fail to interact normally, resulting in the long-known cognitive impairments, ...

How your brain remembers what you had for dinner last night

January 17, 2018
Confirming earlier computational models, researchers at University of California San Diego and UC San Diego School of Medicine, with colleagues in Arizona and Louisiana, report that episodic memories are encoded in the hippocampus ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.