Chromosomal Variation in Neurons of the Developing and Adult Mammalian Nervous System

A basic assumption about the normal nervous system is that its neurons possess identical genomes. Here we present direct evidence for genomic variability, manifested as chromosomal aneuploidy, among developing and mature neurons. Analysis of mouse embryonic cerebral cortical neuroblasts in situ dete...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2001-11, Vol.98 (23), p.13361-13366
Main Authors: Rehen, Stevens Kastrup, McConnell, Michael J., Kaushal, Dhruv, Kingsbury, Marcy A., Yang, Amy H., Chun, Jerold
Format: Article
Language:English
Subjects:
Aneuploidy
Animals
Biological Sciences
Cells
Cerebral Cortex - ultrastructure
Cerebral hemispheres
Chromosomes
Female
Flow Cytometry
Genetic Variation
Genomics
Immunohistochemistry
In Situ Hybridization, Fluorescence
Interphase
Karyotyping
Lymphocytes
Male
Mice
Mice, Inbred BALB C
Nervous system
Neuroblasts
Neurons
Neurons - ultrastructure
Sex chromosomes
Y chromosome
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Summary:A basic assumption about the normal nervous system is that its neurons possess identical genomes. Here we present direct evidence for genomic variability, manifested as chromosomal aneuploidy, among developing and mature neurons. Analysis of mouse embryonic cerebral cortical neuroblasts in situ detected lagging chromosomes during mitosis, suggesting the normal generation of aneuploidy in these somatic cells. Spectral karyotype analysis identified ≈33% of neuroblasts as aneuploid. Most cells lacked one chromosome, whereas others showed hyperploidy, monosomy, and/or trisomy. The prevalence of aneuploidy was reduced by culturing cortical explants in medium containing fibroblast growth factor 2. Interphase fluorescence in situ hybridization on embryonic cortical cells supported the rate of aneuploidy observed by spectral karyotyping and detected aneuploidy in adult neurons. Our results demonstrate that genomes of developing and adult neurons can be different at the level of whole chromosomes.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.231487398