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Articles, Development/Plasticity/Repair

Aneuploid Cells Are Differentially Susceptible to Caspase-Mediated Death during Embryonic Cerebral Cortical Development

Suzanne E. Peterson, Amy H. Yang, Diane M. Bushman, Jurjen W. Westra, Yun C. Yung, Serena Barral, Tetsuji Mutoh, Stevens K. Rehen and Jerold Chun
Journal of Neuroscience 14 November 2012, 32 (46) 16213-16222; DOI: https://doi.org/10.1523/JNEUROSCI.3706-12.2012
Suzanne E. Peterson
1Department of Molecular Biology, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037 and
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Amy H. Yang
1Department of Molecular Biology, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037 and
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Diane M. Bushman
1Department of Molecular Biology, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037 and
2Biomedical Sciences Graduate Program, School of Medicine, University of California San Diego, La Jolla, California 92093
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Jurjen W. Westra
1Department of Molecular Biology, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037 and
2Biomedical Sciences Graduate Program, School of Medicine, University of California San Diego, La Jolla, California 92093
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Yun C. Yung
1Department of Molecular Biology, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037 and
2Biomedical Sciences Graduate Program, School of Medicine, University of California San Diego, La Jolla, California 92093
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Serena Barral
1Department of Molecular Biology, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037 and
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Tetsuji Mutoh
1Department of Molecular Biology, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037 and
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Stevens K. Rehen
1Department of Molecular Biology, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037 and
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Jerold Chun
1Department of Molecular Biology, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, California 92037 and
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Abstract

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.

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The Journal of Neuroscience: 32 (46)
Journal of Neuroscience
Vol. 32, Issue 46
14 Nov 2012
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Aneuploid Cells Are Differentially Susceptible to Caspase-Mediated Death during Embryonic Cerebral Cortical Development
Suzanne E. Peterson, Amy H. Yang, Diane M. Bushman, Jurjen W. Westra, Yun C. Yung, Serena Barral, Tetsuji Mutoh, Stevens K. Rehen, Jerold Chun
Journal of Neuroscience 14 November 2012, 32 (46) 16213-16222; DOI: 10.1523/JNEUROSCI.3706-12.2012

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Aneuploid Cells Are Differentially Susceptible to Caspase-Mediated Death during Embryonic Cerebral Cortical Development
Suzanne E. Peterson, Amy H. Yang, Diane M. Bushman, Jurjen W. Westra, Yun C. Yung, Serena Barral, Tetsuji Mutoh, Stevens K. Rehen, Jerold Chun
Journal of Neuroscience 14 November 2012, 32 (46) 16213-16222; DOI: 10.1523/JNEUROSCI.3706-12.2012
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