Tetraploid development in the mouse

Abstract

Spontaneous duplication of the mammalian genome occurs in approximately 1% of fertilizations. Although one or more whole genome duplications are believed to have influenced vertebrate evolution, polyploidy of contemporary mammals is generally incompatible with normal development and function of all but a few tissues. The production of tetraploid (4n) embryos has become a common experimental manipulation in the mouse. Although development of tetraploid mice has generally not been observed beyond midgestation, tetraploid:diploid (4n:2n) chimeras are widely used as a method for rescuing extraembryonic defects. The tolerance of tissues to polyploidy appears to be dependent on genetic background. Indeed, the recent discovery of a naturally tetraploid rodent species suggests that, in rare genetic backgrounds, mammalian genome duplications may be compatible with the development of viable and fertile adults. Thus, the range of developmental potentials of tetraploid embryos remains in large part unexplored. Here, we review the biological consequences and experimental utility of tetraploid mammals, in particular the mouse. Developmental Dynamics 228:751-766, 2003.

Transient window of resilience during early development minimizes teratogenic effects of heat in zebrafish embryos

“…In diploid zebrafish embryos exposed to transient heat, embryonic lethality after genome doubling can occur early by ∼24 hr postfertilization (hpf) or later by ∼4–5 days postfertilization (dpf). The late larval lethality is expected because a change in ploidy from endogenous diploidy to tetraploidy is incompatible with survival as adults (Snow, 1975; Eakin and Behringer, 2003). The early lethality in zebrafish is reminiscent of the early embryonic lethality seen in mammalian embryos exposed to nonphysiological temperatures (Edwards et al, 1997b; Chambers et al, 1998; Graham et al, 1998; Moretti et al, 2005).…”

Efficient Production of Bovine Tetraploid Embryos by Electrofusion of In Vitro Produced Two-Cell Stage Embryos

“…Several approaches have been employed to produce mammalian tetraploid embryos in vitro [14]. The first approach is to transfer an embryonic nucleus into a fertilized egg, which results in the production of a tetraploid embryo [15].…”

“…The third method is to fuse two diploid blastomeres at the 2-cell stage embryo with either polyethylene glycol (PEG) [18,19], inactivated Sendai virus [20] or by electrofusion. Among these fusion methods, electrofusion is the most widely used tool for the production of tetraploid embryos [1,21,22] as it is safer than the chemical-or virus-mediated methods and more convenient and economical than microsurgical injection [14].…”

Tetraploidy-associated centrosome overduplication in mouse early embryos

“…Tetraploidization (whole genome duplication) because of cell division failure often impairs genome integrity in mammalian somatic cells and potentially leads to tumorigenesis or developmental deficiencies [1–8]. The mechanism via which tetraploidization affects genome integrity and other basic biological processes remains poorly understood.…”

“…This result clearly demonstrates that tetraploidy-driven centrosome overduplication observed in human cancer cell lines also occurs in non-cancer mouse embryonic cells, suggesting the generality of the newly identified pathway of centriole deregulation. Tetraploidization in early embryos usually leads to severe developmental deficiencies in mammalian species [8]; however, the identity of the cellular processes that are affected by tetraploidization remain unclear. Our observation indicates that tetraploidization of early mammalian embryonic cells, even when it occurs prior to centriole possession, damages the subsequent centrosome number control and thereby potentially perturbs the genetic stability of their progenies.

10.1080/19420889.2018.1526605-F0001Figure 1.Frequent generation of the supernumerary centrosome in tetraploidized embryos.(a) A schematic of the experimental procedure.

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