Generation, long-term persistence, and neuronal differentiation of cells with nuclear aberrations in the adult zebrafish brain

• Published in: Neuroscience 2009-04, Vol.159 (4), p.1338-1348
• Main Authors: Zupanc, G.K.H, Wellbrock, U.M, Sîrbulescu, R.F, Rajendran, R.S
• Format: Article
• Language: English
• Subjects: adult neurogenesis; adult stem cells; Adult Stem Cells - cytology; Adult Stem Cells - physiology; anaphase bridge; aneuploidy; Animals; Biological and medical sciences; Brain - cytology; Brain - physiology; Bromodeoxyuridine; Cell Count; Cell Nucleus Shape; Cell Proliferation; Cell Survival - genetics; Chromosome Aberrations; Danio rerio; ELAV Proteins - metabolism; Female; Fundamental and applied biological sciences. Psychology; Immunohistochemistry; laggard; Male; Microscopy, Confocal; Microscopy, Fluorescence; mitotic segregation defect; Neurogenesis - genetics; Neurogenesis - physiology; Neurology; Neurons - cytology; Neurons - physiology; Teleostei; Tyrosine 3-Monooxygenase - metabolism; Vertebrates: nervous system and sense organs; Zebrafish
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2009.02.014

Abstract Zebrafish, like other teleosts, continuously produce new cells in numerous regions of the adult brain. Immunolabeling employing antisera against phosphorylated histone-H3 and 5-bromo-2′-deoxyuridine revealed that approximately 6%–7% of such cells exhibited nuclear aberrations. These aberrations, presumably the result of mitotic segregation defects, included single and multiple laggards (both during metaphase and anaphase) and anaphase bridges. Cells with such aberrations persisted long-term and comprised, when examined 7.5 months after their generation, approximately 2.5% of the total population of adult-born cells. The drop in relative frequency of aberrations in the course of further development appears to be caused by elimination of cells with nuclear aberrations, presumably by apoptotic cell death. The cells with nuclear aberrations that persisted long-term were capable of neuronal differentiation, as demonstrated by combining anti-5-bromo-2′-deoxyuridine immunohistochemistry with immunostaining against the neuronal marker protein Hu or the enzyme tyrosine hydroxylase, a marker of catecholaminergic neurons. We hypothesize that the alterations in chromosome number and/or chromosome structure caused by nuclear aberrations do not necessarily result in loss of vital functions or in tumorigenesis. Instead, cells with such aberrations are able to undergo what appears to be normal development.