Key Mechanism That Regulates The Development Of Stem Cells Into Neurons

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USC Researchers Identify Key Mechanism That Regulates The Development

Of Stem Cells Into Neurons

11 Nov 2008

Researchers at the University of Southern California (USC) have

identified a novel mechanism in the regulation and differentiation of

neural stem cells.

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 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. Jungmook Lyu, Vicky Yamamoto and Wange

Lu. " Cleavage of Wnt Receptor Ryk Regulates Neuronal Differentiation

during Cortical Neurogenesis. " Developmental Cell (Nov. 2008).

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.

University of Southern California

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Article URL: http://www.medicalnewstoday.com/articles/128909.php