PMID- 23637172
OWN - NLM
STAT- MEDLINE
DCOM- 20130701
LR  - 20220309
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 33
IP  - 18
DP  - 2013 May 1
TI  - Inactivation of mTORC1 in the developing brain causes microcephaly and affects 
      gliogenesis.
PG  - 7799-810
LID - 10.1523/JNEUROSCI.3294-12.2013 [doi]
AB  - The mammalian target of rapamycin (mTOR) regulates cell growth in response to 
      various intracellular and extracellular signals. It assembles into two 
      multiprotein complexes: the rapamycin-sensitive mTOR complex 1 (mTORC1) and the 
      rapamycin-insensitive mTORC2. In this study, we inactivated mTORC1 in mice by 
      deleting the gene encoding raptor in the progenitors of the developing CNS. Mice 
      are born but never feed and die within a few hours. The brains deficient for 
      raptor show a microcephaly starting at E17.5 that is the consequence of a reduced 
      cell number and cell size. Changes in cell cycle length during late cortical 
      development and increased cell death both contribute to the reduction in cell 
      number. Neurospheres derived from raptor-deficient brains are smaller, and 
      differentiation of neural progenitors into glia but not into neurons is 
      inhibited. The differentiation defect is paralleled by decreased Stat3 signaling, 
      which is a target of mTORC1 and has been implicated in gliogenesis. Together, our 
      results show that postnatal survival, overall brain growth, and specific aspects 
      of brain development critically depend on mTORC1 function.
FAU - Cloetta, Dimitri
AU  - Cloetta D
AD  - Biozentrum, University of Basel, CH-4056 Basel, Switzerland.
FAU - Thomanetz, Venus
AU  - Thomanetz V
FAU - Baranek, Constanze
AU  - Baranek C
FAU - Lustenberger, Regula M
AU  - Lustenberger RM
FAU - Lin, Shuo
AU  - Lin S
FAU - Oliveri, Filippo
AU  - Oliveri F
FAU - Atanasoski, Suzana
AU  - Atanasoski S
FAU - Ruegg, Markus A
AU  - Ruegg MA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Intermediate Filament Proteins)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Nes protein, mouse)
RN  - 0 (Nestin)
RN  - 0 (Proteins)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
RN  - 0 (Transcription Factors)
RN  - 0 (Tubulin)
RN  - 0 (beta3 tubulin, mouse)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.4.22.- (Caspase 3)
RN  - G34N38R2N1 (Bromodeoxyuridine)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Apoptosis/genetics
MH  - *Brain/embryology/growth & development/pathology
MH  - Bromodeoxyuridine/metabolism
MH  - Caspase 3/metabolism
MH  - Cell Cycle/genetics
MH  - Cell Differentiation/*genetics
MH  - Cell Proliferation
MH  - Disease Models, Animal
MH  - Embryo, Mammalian
MH  - Female
MH  - Gene Expression Regulation, Developmental/*genetics
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Intermediate Filament Proteins/genetics/metabolism
MH  - Male
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Mice
MH  - Mice, Knockout
MH  - Microcephaly/*genetics/mortality/*pathology
MH  - Multiprotein Complexes
MH  - Nerve Tissue Proteins/genetics/metabolism
MH  - Nestin
MH  - Neuroglia/*pathology
MH  - Proteins/genetics/*metabolism
MH  - STAT3 Transcription Factor/metabolism
MH  - TOR Serine-Threonine Kinases
MH  - Transcription Factors/genetics/metabolism
MH  - Tubulin/metabolism
PMC - PMC6618947
EDAT- 2013/05/03 06:00
MHDA- 2013/07/03 06:00
PMCR- 2013/11/01
CRDT- 2013/05/03 06:00
PHST- 2013/05/03 06:00 [entrez]
PHST- 2013/05/03 06:00 [pubmed]
PHST- 2013/07/03 06:00 [medline]
PHST- 2013/11/01 00:00 [pmc-release]
AID - 33/18/7799 [pii]
AID - 3294-12 [pii]
AID - 10.1523/JNEUROSCI.3294-12.2013 [doi]
PST - ppublish
SO  - J Neurosci. 2013 May 1;33(18):7799-810. doi: 10.1523/JNEUROSCI.3294-12.2013.