MCCONNELL, M.J.*; REHEN, S.K.; KAUSHAL, D.; KINGSBURY, M.A.; YANG, A.H.; CHUN, J.: Genetic Mosaicism During Mammalian Neurogenesis

The mammalian central nervous system is composed of a diverse array of cell types. It is thought that this diversity arises from transcriptional and post-transcriptional modification of large gene families from a constant genome. Using fluorescence immunohistochemistry on embryonic brain, we observed chromosome segregation defects, often associated with aneuploidy in tumor cell lines, in progenitor neuroblasts from normal mice. We therefore examined chromosomal number in embryonic neuroblasts. Spectral karyotyping (SKY) was used to observe mitotic neuroblast chromosomes from embryonic cortex, and combined with flow cytometry to measure the mean cellular DNA content of cells within the embryonic cortex. In addition, sex chromosome “paint” hybridization probes were used to detect chromosome gain and loss in interphase cortical cells from embryonic and adult male mice. These distinctly different approaches all supported a single conclusion: aneuploidy exists amongst developing and mature mammalian neurons. While aneuploidy may account for known neuroblast cell death, the existence of aneuploid neurons in adult cortex suggests that at least some aneuploid cells survive through development, and/or are created in adults. The existence of aneuploid neurons implicates genomic differences amongst somatic cells of the brain. This form of genetic mosaicism may have influences on multiple aspects of neural development and function.