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Tissue-Specific Stem Cells
Article first published online: 24 FEB 2011
Copyright © 2010 AlphaMed Press
Volume 29, Issue 2, pages 320–331, February 2011
How to Cite
Moon, B.-S., Kim, H.-Y., Kim, M.-Y., Yang, D.-H., Lee, J.-M., Cho, K.-W., Jung, H.-S. and Choi, K.-Y. (2011), Sur8/Shoc2 Involves Both Inhibition of Differentiation and Maintenance of Self-Renewal of Neural Progenitor Cells via Modulation of Extracellular Signal-Regulated Kinase Signaling. STEM CELLS, 29: 320–331. doi: 10.1002/stem.586
Author contributions: B.-S.M.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; H.-Y.K.: manuscript writing, data analysis and interpretation; M.-Y.K.: manuscript writing, data analysis and interpretation; D.-H.Y.: manuscript writing, conception and design; J.-M.L.: provision of study material or patients; K.-W.C.: provision of study material or patients; H.-S.J.: provision of study material or patients; K.-Y.C.: financial support, conception and design, data analysis and interpretation, manuscript writing, final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS December 23, 2011.
- Issue published online: 24 FEB 2011
- Article first published online: 24 FEB 2011
- Accepted manuscript online: 23 DEC 2010 01:21PM EST
- Manuscript Accepted: 1 DEC 2010
- Manuscript Received: 20 JUL 2010
- National Research Foundation (NRF) funded by the Ministry of Education, Science, and Technology of Korea (the Translational Research Center for Protein Function Control. Grant Number: 2009-0083522
- Stem Cell Research Project. Grant Number: 2010-0020235
- ERK signaling;
- Neural stem cells;
- Scaffold protein
Sur8/Shoc2 is a scaffold protein that regulates the Ras-extracellular signal-regulated kinase (ERK) pathway. However, the roles of Sur8 in cellular physiologies are poorly understood. In this study, Sur8 was severely repressed in the course of neural progenitor cell (NPC) differentiation in the cerebral cortex of developing rat embryos. Similarly, Sur8 was also critically reduced in cultured NPCs, which were induced differentiation by removal of basic fibroblast growth factor (bFGF). Sur8 regulation occurs at the protein level rather than at the mRNA level as revealed by both in situ hybridization and reverse transcriptase polymerase chain reaction analyses. The role of Sur8 in NPC differentiation was confirmed by lentivirus-mediated Sur8 knockdown, which resulted in increased differentiation, whereas exogenous expression of Sur8 inhibited differentiation. Contrastingly, NPC proliferation was promoted by overexpression, but was suppressed by Sur8 knockdown. The role of Sur8 as an antidifferentiation factor in the developing rat brain was confirmed by an ex vivo embryo culture system combined with the lentivirus-mediated Sur8 knockdown. The numbers and sizes of neurospheres were reduced, but neuronal outgrowth was enhanced by the Sur8 knockdown. The Ras-ERK pathway is involved in Sur8-mediated regulations of differentiation, as the treatment of ERK kinase (MEK) inhibitors blocks the effects of Sur8. The regulations of NPCs' differentiation and proliferation by the Ras-ERK pathway were also shown by the rescues of the effects of bFGF depletion, neuronal differentiation, and antiproliferation by epidermal growth factor. In summary, Sur8 is an antidifferentiation factor that stimulates proliferation for maintenance of self-renewal in NPCs via modulation of the Ras-ERK pathway. STEM CELLS 2011; 29:320–331