RT Journal Article
SR Electronic
T1 Aneuploid Cells Are Differentially Susceptible to Caspase-Mediated Death during Embryonic Cerebral Cortical Development
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 16213
OP 16222
DO 10.1523/JNEUROSCI.3706-12.2012
VO 32
IS 46
A1 Suzanne E. Peterson
A1 Amy H. Yang
A1 Diane M. Bushman
A1 Jurjen W. Westra
A1 Yun C. Yung
A1 Serena Barral
A1 Tetsuji Mutoh
A1 Stevens K. Rehen
A1 Jerold Chun
YR 2012
UL http://www.jneurosci.org/content/32/46/16213.abstract
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.