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PNAS | November 6, 2001 | vol. 98 | no. 23 | 13361-13366
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Neurobiology
 Chromosomal variation in neurons of the developing and adult mammalian nervous system

Stevens Kastrup Rehen*,dagger , Michael J. McConnell*,dagger ,Dagger , Dhruv Kaushal*,dagger ,§, Marcy A. Kingsbury*, Amy H. Yang*,Dagger , and Jerold Chun*,Dagger ,§,

* Department of Pharmacology and § Neurosciences and Dagger  Biomedical Sciences Programs, School of Medicine, University of California, San Diego, CA 92093-0636

Communicated by Edward M. Scolnick, Merck & Company, Inc., West Point, PA, September 17, 2001 (received for review July 30, 2001)

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 approx 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.

dagger S.K.R., M.J.M., and D.K. contributed equally to this work.

To whom reprint requests should be addressed at the present address: Department of Molecular Neuroscience, Merck Research Laboratories, San Diego, 3535 General Atomics Court, San Diego, CA 92121. E-mail: jerold_chun{at}merck.com.

www.pnas.org/cgi/doi/10.1073/pnas.231487398
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