PMID- 20876733
OWN - NLM
STAT- MEDLINE
DCOM- 20101116
LR  - 20211203
IS  - 1549-5477 (Electronic)
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 24
IP  - 20
DP  - 2010 Oct 15
TI  - Neurofibromatosis-1 regulates neuroglial progenitor proliferation and glial 
      differentiation in a brain region-specific manner.
PG  - 2317-29
LID - 10.1101/gad.1957110 [doi]
AB  - Recent studies have shown that neuroglial progenitor/stem cells (NSCs) from 
      different brain regions exhibit varying capacities for self-renewal and 
      differentiation. In this study, we used neurofibromatosis-1 (NF1) as a model 
      system to elucidate a novel molecular mechanism underlying brain region-specific 
      NSC functional heterogeneity. We demonstrate that Nf1 loss leads to increased NSC 
      proliferation and gliogenesis in the brainstem, but not in the cortex. Using Nf1 
      genetically engineered mice and derivative NSC neurosphere cultures, we show that 
      this brain region-specific increase in NSC proliferation and gliogenesis results 
      from selective Akt hyperactivation. The molecular basis for the increased 
      brainstem-specific Akt activation in brainstem NSCs is the consequence of 
      differential rictor expression, leading to region-specific mammalian target of 
      rapamycin (mTOR)/rictor-mediated Akt phosphorylation and Akt-regulated p27 
      phosphorylation. Collectively, these findings establish mTOR/rictor-mediated Akt 
      activation as a key driver of NSC proliferation and gliogenesis, and identify a 
      unique mechanism for conferring brain region-specific responses to cancer-causing 
      genetic changes.
FAU - Lee, Da Yong
AU  - Lee DY
AD  - Department of Neurology, Washington University School of Medicine, St. Louis, 
      Missouri 63110, USA.
FAU - Yeh, Tu-Hsueh
AU  - Yeh TH
FAU - Emnett, Ryan J
AU  - Emnett RJ
FAU - White, Crystal R
AU  - White CR
FAU - Gutmann, David H
AU  - Gutmann DH
LA  - eng
GR  - R01 NS065547/NS/NINDS NIH HHS/United States
GR  - R21 NS058433/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100928
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (Carrier Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Neurofibromin 1)
RN  - 0 (Rapamycin-Insensitive Companion of mTOR Protein)
RN  - 0 (rictor protein, mouse)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
CIN - Genes Dev. 2010 Oct 15;24(20):2233-8. PMID: 20952533
MH  - Animals
MH  - Blotting, Western
MH  - Brain/cytology/*metabolism
MH  - Brain Stem/cytology/metabolism
MH  - Carrier Proteins/metabolism
MH  - *Cell Differentiation
MH  - *Cell Proliferation
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology/metabolism
MH  - Female
MH  - Immunohistochemistry
MH  - Intracellular Signaling Peptides and Proteins/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neurofibromin 1/genetics/*metabolism
MH  - Neurogenesis
MH  - Neuroglia/cytology
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rapamycin-Insensitive Companion of mTOR Protein
MH  - Stem Cells/cytology/metabolism
MH  - TOR Serine-Threonine Kinases
PMC - PMC2956210
EDAT- 2010/09/30 06:00
MHDA- 2010/11/17 06:00
PMCR- 2011/04/15
CRDT- 2010/09/30 06:00
PHST- 2010/09/30 06:00 [entrez]
PHST- 2010/09/30 06:00 [pubmed]
PHST- 2010/11/17 06:00 [medline]
PHST- 2011/04/15 00:00 [pmc-release]
AID - gad.1957110 [pii]
AID - 10.1101/gad.1957110 [doi]
PST - ppublish
SO  - Genes Dev. 2010 Oct 15;24(20):2317-29. doi: 10.1101/gad.1957110. Epub 2010 Sep 
      28.