Mitotic polyploidization of mouse heart myocytes during the first postnatal week

Abstract

Polyploidization of myocytes in the cardiac ventricle of mice occurs predominantly during the first week of the postnatal life. Using isolated cells it was shown that about 70% of the cardiomyocytes become binuclear at this time (2c x 2), while 10% are mononuclear but contain 4c of DNA, where c was the haploid level of DNA. About 2% of the cell population were reprsented by 4c x 2 or 8c cells. Cytophotometry of Feulgen-stained DNA in 14C-thymidine-labeled nuclei has shown that the cells that enter the mitotic cycle are mainly diploid. After mitosis (30 h or more after thymidine application) the label was found predominantly in 2c x 2 and 4c cell types. Comparison of the curves presenting dynamics of labeled mitoses and the accumulation of labeled binuclear cells reveals that binuclear 2c x 2 cells are formed by acytokinetic mitosis. The formation of 4c mononuclear cells is accomplished via other types of mitotic arrest; this may be due, for example, to a block in the pro- or metaphase. Only very rare cases of cytotomy were detected and the number of newly formed 2c cells was very low. It is concluded that cell multiplication is practically arrested at this period of life, and growth of the ventricular mass is due to polyploidization of virtually all cycling cells, while their number remains unchanged. Mechanisms and functional significance cardiomyocyte polyploidization are discussed.

Death through a tragedy: mitotic catastrophe

“…Notably, features reminiscent of MC have been observed during normal development. Similar sequence of polyploidization events have been described during the development of trophoblast, 125 and of heart myocytes during the first postnatal week, 126 and during reproduction of gland cells and neurons. 127 These observations suggest that MC cannot be considered a simple dysregulation process activated in response to DNA damage but rather represents an example of a programmed event.…”

Tissue-specific control of midbody microtubule stability by Citron kinase through modulation of TUBB3 phosphorylation

“…A striking example of this possibility is the progressive accumulation of myofibrils and intermediate filaments in proliferating cardiomyocytes, ending with abortive cytokinesis and accumulation of binucleated cells during the early postnatal period of heart development. 50,51 Therefore, it is conceivable that specific mechanisms may have evolved to cope with the modifications of cytoskeleton that could inhibit cytokinesis in some differentiating cell types. The case of CIT-K is a so far a unique example of how cytokinesis of specific cells can be affected by the lack of a particular protein.…”

Analysis of cell ploidy in histological sections of mouse tissues by DNA-DNA in situ hybridization with digoxigenin-labelled probes

“…lc, Table 2). Brodsky et al (1980) showed that cells in the mouse myocardium were mostly binucleate and about 10% of the nuclei were polyploid, although in some cases the frequency of polyploid nuclei "Tissues from mice of various crosses as indicated in the text. 63:1 is ethanol: acetic acid (3:1 v/v) fixative, and PFA is 4% paraformaldehyde.…”