Neurobiological surprise: Fish brain cells with marked aberrations in chromosome number develop into neurons capable of long-term survival

Günther Zupanc, Jacobs Professor of Neurobiology, for the first time provided evidence that even a profound deviation from the number of chromosomes typical for a species does not necessarily result in programmed death of the cells affected or in physiological and behavioural deficiencies of the organism. Analysis of the brain of adult healthy knifefish, in which every fifth newly formed cell markedly deviates from the “normal” number of chromosomes, showed that the aberrant cells can develop into neurons with a long-term survival until the organism’s natural death. The study is published in the current issue of Developmental Neurobiology (68: S. 1257–1268, 2008)

[ Aug 15, 2008]  Established scientific doctrine for a long time has assumed that every cell of an organism contains identical genetic information encoded by a species-specific number of chromosomes, with the exception of sperms and eggs with half the number. Humans, for example, have 46 in total, 22 pairs of autosomal chromosomes and two sex chromosomes. Aberration from the regular number, so-called aneuploidy, was thought to usually result in either the elimination of affected cells by programmed cell death or in severe diseases. Down Syndrome, for instance, which is caused by the presence of an extra 21st chromosome in all, or part of the, body’s cells, leads to physical and mental disabilities in humans; and recent studies showed that most, if not all, malignant tumors exhibit marked variations in chromosome number among their cells.

Günther Zupanc, together with his research group at Jacobs University, now provided evidence that the rate of programmed cell death in brain cells of the brown ghost knifefish Apteronotus leptorhynchus only marginally differs between cells with normal and aberrant chromosome numbers, the relative numbers being slightly higher in the latter category. Like other teleost fish, this species is distinguished by its enormous potential to continuously produce new neurons in the adult brain. The relatively high fraction of aneuploid cells originates from segregation defects during mitotic cell division. Long-term survival of cells with mitotic segregation defects could be demonstrated to last until the natural death of the fishes. In the experiments the oldest neurons with aberrant chromosome numbers found were 860 days old, which is equivalent to half the species’ life expectancy. Moreover, among the long-term persistent cells with mitotic segregation defects a similar portion developed into neurons as did among the long-term persistent cells without such defects.

“The results of our research really took us by surprise,” Günther Zupanc comments. In his opinion, the morphologically and immunologically normal appearance of the aneuploid neuronal cells and their survival for the greater part of the fish’s lifespan support the notion that the loss or gain of chromosomes provides a regular control mechanism of gene expression during the normal development of organisms. “Our results therefore raise some very significant questions: Is aneuploidy really the cause for cancer? Or are the fish equipped with a special mechanism that protects aneuploid cells from the normal fate to become cancerous? The latter idea is really fascinating as it suggests new strategies of cancer control,” concludes the neurobiologist from Jacobs University.