PMID- 23152605
OWN - NLM
STAT- MEDLINE
DCOM- 20130121
LR  - 20211021
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 32
IP  - 46
DP  - 2012 Nov 14
TI  - Aneuploid cells are differentially susceptible to caspase-mediated death during 
      embryonic cerebral cortical development.
PG  - 16213-22
LID - 10.1523/JNEUROSCI.3706-12.2012 [doi]
AB  - Neural progenitor cells, neurons, and glia of the normal vertebrate brain are 
      diversely aneuploid, forming mosaics of intermixed aneuploid and euploid cells. 
      The functional significance of neural mosaic aneuploidy is not known; however, 
      the generation of aneuploidy during embryonic neurogenesis, coincident with 
      caspase-dependent programmed cell death (PCD), suggests that a cell's karyotype 
      could influence its survival within the CNS. To address this hypothesis, PCD in 
      the mouse embryonic cerebral cortex was attenuated by global pharmacological 
      inhibition of caspases or genetic removal of caspase-3 or caspase-9. The 
      chromosomal repertoire of individual brain cells was then assessed by chromosome 
      counting, spectral karyotyping, fluorescence in situ hybridization, and DNA 
      content flow cytometry. Reducing PCD resulted in markedly enhanced mosaicism that 
      was comprised of increased numbers of cells with the following: (1) numerical 
      aneuploidy (chromosome losses or gains); (2) extreme forms of numerical 
      aneuploidy (>5 chromosomes lost or gained); and (3) rare karyotypes, including 
      those with coincident chromosome loss and gain, or absence of both members of a 
      chromosome pair (nullisomy). Interestingly, mildly aneuploid (<5 chromosomes lost 
      or gained) populations remained comparatively unchanged. These data demonstrate 
      functional non-equivalence of distinguishable aneuploidies on neural cell 
      survival, providing evidence that somatically generated, cell-autonomous genomic 
      alterations have consequences for neural development and possibly other brain 
      functions.
FAU - Peterson, Suzanne E
AU  - Peterson SE
AD  - Department of Molecular Biology, Dorris Neuroscience Center, The Scripps Research 
      Institute, La Jolla, California 92037, USA.
FAU - Yang, Amy H
AU  - Yang AH
FAU - Bushman, Diane M
AU  - Bushman DM
FAU - Westra, Jurjen W
AU  - Westra JW
FAU - Yung, Yun C
AU  - Yung YC
FAU - Barral, Serena
AU  - Barral S
FAU - Mutoh, Tetsuji
AU  - Mutoh T
FAU - Rehen, Stevens K
AU  - Rehen SK
FAU - Chun, Jerold
AU  - Chun J
LA  - eng
GR  - R21 MH076145/MH/NIMH NIH HHS/United States
GR  - T32 GM007752/GM/NIGMS NIH HHS/United States
GR  - MH076145/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Amino Acid Chloromethyl Ketones)
RN  - 0 (benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone)
RN  - 9007-49-2 (DNA)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 9)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Amino Acid Chloromethyl Ketones/pharmacology
MH  - *Aneuploidy
MH  - Animals
MH  - Apoptosis/physiology
MH  - Caspase 3/genetics/physiology
MH  - Caspase 9/genetics/physiology
MH  - Caspases/*physiology
MH  - Cell Death/*physiology
MH  - Cerebral Cortex/cytology/*embryology/enzymology
MH  - DNA/biosynthesis/genetics
MH  - Female
MH  - Flow Cytometry
MH  - Genotype
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
MH  - Male
MH  - Metaphase/drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mitosis/physiology
MH  - Pregnancy
MH  - Sex Determination Processes/physiology
PMC - PMC3614491
MID - NIHMS421774
EDAT- 2012/11/16 06:00
MHDA- 2013/01/23 06:00
PMCR- 2013/05/14
CRDT- 2012/11/16 06:00
PHST- 2012/11/16 06:00 [entrez]
PHST- 2012/11/16 06:00 [pubmed]
PHST- 2013/01/23 06:00 [medline]
PHST- 2013/05/14 00:00 [pmc-release]
AID - 32/46/16213 [pii]
AID - 3807793 [pii]
AID - 10.1523/JNEUROSCI.3706-12.2012 [doi]
PST - ppublish
SO  - J Neurosci. 2012 Nov 14;32(46):16213-22. doi: 10.1523/JNEUROSCI.3706-12.2012.