Apoptotic cell death, long-term persistence, and neuronal differentiation of aneuploid cells generated in the adult brain of teleost fish.

Aneuploidy, caused by segregation defects during mitosis, has previously been identified in adult-born cells of mammals and teleosts. In the present study, we have examined the fate of these cells in the brain of the teleost fish Apteronotus leptorhynchus. By immunostaining against active caspase-3, we have shown that both cells with normal nuclear morphology and cells with mitotic segregation defects undergo apoptosis, but the relative number of apoptotic cells is higher among cells of the latter category. Long-term survival of cells with mitotic segregation defects could be demonstrated by incorporation of 5-bromo-2'-deoxyuridine into newly synthesized DNA during the S-phase of mitosis, and by employment of postadministration survival times of up to 860 days. Moreover, by combining 5-bromo-2'-deoxyuridine immunolabeling with immunostaining against the neuron-specific marker protein Hu, we have shown that among the long-term persistent cells with mitotic segregation defects a similar portion develops into neurons as does among the long-term persistent cells without such defects. It is possible that aneuploid cells play a role in the regulation of gene expression by somatic genomic alterations during postnatal development.