Chromosomal variation in neurons of the developing and adult mammalian nervous system

A basic assumption about the normal nervous system is that its neurons poss ess identical genomes. Here we present direct evidence for genomic variabil ity, manifested as chromosomal aneuploidy, among developing and mature neur ons. Analysis of mouse embryonic cerebral cortical neuroblasts in situ dete cted lagging chromosomes during mitosis, suggesting the normal generation o f aneuploidy in these somatic cells. Spectral karyotype analysis identified approximate to 33% of neuroblasts as aneuploid. Most cells lacked one chro mosome, whereas others showed hyperploidy, monosomy, and/or trisomy. The pr evalence of aneuploidy was reduced by culturing cortical explants in medium containing fibroblast growth factor 2. Interphase fluorescence in situ hyb ridization on embryonic cortical cells supported the rate of aneuploidy obs erved by spectral karyotyping and detected aneuploidy in adult neurons. Our results demonstrate that genomes of developing and adult neurons can be di fferent at the level of whole chromosomes.