Sur8/Shoc2 involves both inhibition of differentiation and maintenance of self-renewal of neural progenitor cells via modulation of extracellular signal-regulated kinase signaling

Byoung San Moon, Hyun Yi Kim, Mi Yeon Kim, Dong Hwa Yang, Jong Min Lee, Kyoung Won Cho, Hansung Jung, Kang-Yell Choi

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Sur8/Shoc2 is a scaffold protein that regulates the Rasextracellular 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.

Original languageEnglish
Pages (from-to)320-331
Number of pages12
JournalStem Cells
Volume29
Issue number2
DOIs
Publication statusPublished - 2011 Feb 1

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MAP Kinase Signaling System
Extracellular Signal-Regulated MAP Kinases
Stem Cells
Lentivirus
Fibroblast Growth Factor 2
Cell Differentiation
Embryonic Structures
MAP Kinase Kinase Kinases
Reverse Transcriptase Polymerase Chain Reaction
Epidermal Growth Factor
Cerebral Cortex
In Situ Hybridization
Proteins
Phosphotransferases
Cell Proliferation
Messenger RNA
Brain

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

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title = "Sur8/Shoc2 involves both inhibition of differentiation and maintenance of self-renewal of neural progenitor cells via modulation of extracellular signal-regulated kinase signaling",
abstract = "Sur8/Shoc2 is a scaffold protein that regulates the Rasextracellular 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.",
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Sur8/Shoc2 involves both inhibition of differentiation and maintenance of self-renewal of neural progenitor cells via modulation of extracellular signal-regulated kinase signaling. / Moon, Byoung San; Kim, Hyun Yi; Kim, Mi Yeon; Yang, Dong Hwa; Lee, Jong Min; Cho, Kyoung Won; Jung, Hansung; Choi, Kang-Yell.

In: Stem Cells, Vol. 29, No. 2, 01.02.2011, p. 320-331.

Research output: Contribution to journalArticle

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AU - Moon, Byoung San

AU - Kim, Hyun Yi

AU - Kim, Mi Yeon

AU - Yang, Dong Hwa

AU - Lee, Jong Min

AU - Cho, Kyoung Won

AU - Jung, Hansung

AU - Choi, Kang-Yell

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N2 - Sur8/Shoc2 is a scaffold protein that regulates the Rasextracellular 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.

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