How do humans and other mammals get so brainy? USC researcher Wange Lu and his colleagues shed new light on this question in a paper published in the journal Cell Reports on Oct. 24.
The researchers donned their thinking caps to explain how neural stem and progenitor cells differentiate into neurons and related cells called glia. Neurons transmit information through electrical and chemical signals; glia surround, support and protect neurons in the brain and throughout the nervous system. Glia do everything from holding neurons in place to supplying them with nutrients and oxygen to protect them from pathogens.
By studying the embryo neural stem cells of mice in a petri dish, Lu and his colleagues discovered that a protein called SMEK1 promotes the differentiation of neural stem and progenitor cells. At the same time, SMEK1 keeps these cells in check by suppressing their uncontrolled proliferation.
The researchers also determined that SMEK1 doesn’t act alone: It works in concert with Protein Phosphatase 4 to suppress the activity of PAR3, a third protein that discourages neurogenesis — the birth of new neurons. With PAR3 out of the picture, neural stem cells and progenitors are free to differentiate into new neurons and glia.
“These studies reveal the mechanisms of how the brain keeps the balance of stem cells and neurons when the brain is formed,” said Wange Lu, associate professor of biochemistry and molecular biology at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC. “If this process goes wrong, it leads to cancer or mental retardation or other neurological diseases.”
Neural stem and progenitor cells offer tremendous promise as a future treatment for neurodegenerative disorders, and understanding their differentiation is the first step toward harnessing the cells’ therapeutic potential. This could offer new hope for patients with Alzheimer’s, Parkinson’s and many other currently incurable diseases.
Notes about this neurogenetics research
Co-authors from the Broad Center included Vicky Yamamoto, Si Ho Choi and Zhong Wei. Co-authors Hee-Ryang Kim and Choun-Ki Joo work at the Catholic University of Korea in Seoul, and first author Jungmook Lyu is affiliated with both institutions.
Funding for the study came from the National Institutes of Health (grant number 5R01NS067213).
Written by Cristy Lytal
Contact: Cristy Lytal – USC
Source: USC press release
Image Source: The image is credited to Wange Lu/USC, and is adapted from the press release. The image also appears in the Cell Reports research paper.
Original Research: Full open access research for “Protein Phosphatase 4 and Smek Complex Negatively Regulate Par3 and Promote Neuronal Differentiation of Neural Stem/Progenitor Cells” by Jungmook Lyu, Hee-Ryang Kim, Vicky Yamamoto, Si Ho Choi, Zong Wei, Choun-Ki Joo, and Wange Lu in Cell Reports. Published online October 24 2013 doi:10.1016/j.celrep.2013.09.034
