Researchers identify key mechanism regulating neural stem cell development
Photo by Mark Berndt
Researchers found that the protein receptor Ryk has a key role in the differentiation of neural stem cells, and demonstrated a signaling mechanism that regulates neuronal differentiation as stem cells begin to grow into neurons. The study will be published in the Nov. 11 issue of the journal Developmental Cell, and is now available online.
The findings could have important implications for regenerative medicine and cancer therapies, says Wange Lu, Ph.D., assistant professor of biochemistry and molecular biology at the Keck School of Medicine of USC, and the principal investigator on the study.
“Neural stem cells can potentially be used for cell-replacement therapy for neurodegenerative diseases such as Alzheimer’s and Parkinson’s Disease, as well as spinal cord injury,” Lu says. “Knowledge gained from this study will potentially help to generate neurons for such therapy. This knowledge can also be used to inhibit the growth of brain cancer stem cells.”
During brain development, neural stem cells respond to the surrounding environment by either proliferation or differentiation, but the molecular mechanisms underlying the development of neural stem cells and neurons are unclear, Lu notes.
Ryk functions as a receptor of Wnt proteins required for cell-fate determination, axon guidance and neurite outgrowth in organisms. Researchers at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC analyzed sections of the forebrain in animal model embryos to investigate Ryk’s function in vivo.
They found that during neurogenesis, when neural stem cells start to grow into neurons, Ryk protein is cleaved and translocates to the cell nucleus to regulate neuronal differentiation.
This finding is extremely important for understanding the regulation of self-renewal and differentiation of neural stem cells, Lu says. Previous research has shown that Ryk functions as a receptor of Wnt proteins. However, the role of Ryk in neural stem cells and the molecular mechanism of Ryk signaling have not previously been known.
“This study will help in our efforts to produce nerve cells from embryonic stem cells, and may lead to the development of new strategies for the repair of the nervous system, using protein or small molecule therapeutic agents,” says Martin Pera, Ph.D., director of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC.
Further research is needed to explore how Ryk regulates neuronal gene expression, Lu says. Researchers are now expanding their research to studies of differentiation of human embryonic stem cells Into neural stem cells and neurons. These studies are very important for regenerative medicine and drug discovery for therapy of neurodegenerative diseases.
The study was funded by the Baxter Foundation and the American Cancer Society. The current studies using human ES cells are being funded by a CIRM SEED grant.
About the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC Currently housed in the Zilkha Neurological Institute on USC’s Health Sciences campus, the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC is a premier science and research project that pursues investigation into the biological mechanisms that control stem cell behavior. Its scientists work independently and in collaboration with teams from other regional institutes to focus on basic research programs; develop novel platforms in imaging, bioengineering and nanotechnology for application to stem cell research; and translate this work into new therapies for a wide variety of diseases and conditions.
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The Chronicle of Higher Education mentioned USC’s $6 billion fundraising campaign. The story noted that USC had already raised $1 billion in a “quiet phase,” including the $200 million naming gift from USC Trustee and alumnus David Dornsife and wife Dana Dornsife to the USC Dornsife College.
The Guardian (U.K.) highlighted two major gifts to USC in a list of the 10 biggest philanthropic benefactors in America. The list included the $200 million naming gift from USC Trustee and alumnus David Dornsife and wife Dana Dornsife to the USC Dornsife College, and the $110 million gift from USC Trustee and USC Viterbi School alumnus John Mork and wife Julie to create the USC Mork Family Scholars Program.
The New York Times featured the USC U.S.-China Institute documentary “Assignment: China — The Week that Changed the World.” The documentary, part of a series, examines media coverage of the 1972 Nixon trip that reshaped U.S.-China relations after a quarter century of isolation and hostility. “People look back now and take it for granted that the outcome was preordained,” said the institute’s Mike Chinoy, who produced the documentary. Voice of America also featured the story.
Los Angeles Times featured the Oscar Senti-meter, a tool developed by the USC Annenberg School, Los Angeles Times and IBM that analyzes thousands of tweets about the Academy Awards nominees. The story noted that Mexican actor Demian Bechir received an enormous boost on Twitter the day of the nominations, with a total of 6,893 tweets mentioning him, a 47-fold increase from the day before. The story noted the tool uses language-recognition technology developed in collaboration with USC Viterbi School’s Signal Analysis and Interpretation Lab.
The Times of India (India) featured a three-day medical emergency training workshop organized in association with USC. At the workshop, held at GCS Medical College in India, 50 doctors and more than 100 paramedics learned how to improve emergency support systems. William Mallon of the Keck School of USC said that discussion topics included the use of portable ultrasonic devices to scan patients. “The ultrasound applications help physicians make accurate and timely decisions,” he noted. Daily News & Analysis (India) also featured the workshop.
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