Gene Expression in Pre-MBT Embryos and Activation of Maternally-Inherited Program of Apoptosis to be Executed at around MBT as a Fail-Safe Mechanism inXenopusEarly Embryogenesis

Abstract

S-adenosylmethionine decarboxylase (SAMDC) is an enzyme which converts S-adenosylmethione (SAM), a methyl donor, to decarboxylated SAM (dcSAM), an aminopropyl donor for polyamine biosynthesis. In our studies on gene expression control in Xenopus early embryogenesis, we cloned the mRNA for Xenopus SAMDC, and overexpressed the enzyme by microinjecting its mRNA into Xenopus fertilized eggs. In the mRNA-injected embryos, the level of SAMDC was enormously increased, the SAM was exhausted, and protein synthesis was greatly inhibited, but cellular polyamine content did not change appreciably. SAMDC-overexpressed embryos cleaved and developed normally up to the early blastula stage, but at the midblastula stage, or the stage of midblastula transition (MBT), all the embryos were dissociated into cells, and destroyed due to execution of apoptosis. During cleavage SAMDC-overexpressed embryos transcribed caspase-8 gene, and this was followed by activation of caspase-9. When we overexpressed p53 mRNA in fertilized eggs, similar apoptosis took place at MBT, but in this case, transcription of caspase-8 did not occur, however activation of caspase-9 took place. Apoptosis induced by SAMDC-overexpression was completely suppressed by Bcl-2, whereas apoptosis induced by p53 overexpression or treatments with other toxic agents was only partially rescued. When we injected SAMDC mRNA into only one blastomere of 8- to 32-celled embryos, descendant cells of the mRNA-injected blastomere were segregated into the blastocoel and underwent apoptosis within the blastocoel, although such embryos continued to develop and became tadpoles with various extents of anomaly, reflecting the developmental fate of the eliminated cells. Thus, embryonic cells appear to check themselves at MBT and if physiologically severely-damaged cells occur, they are eliminated from the embryo by activation and execution of the maternally-inherited program of apoptosis. We assume that the apoptosis executed at MBT is a “fail-safe” mechanism of early development to save the embryo from accidental damages that take place during cleavage.

Glucocorticoid receptor activation following elevated oocyte cortisol content is associated with zygote activation, early embryo cell division, and IGF system gene responses in rainbow trout

“…It is not clear at this point how that may occur, and it would appear to contradict the currently held view that the zygotic transcriptome is relatively stable and necessary for the regulation of the first cell division. However, there is evidence in several species for differential destabilization of a subset of mRNAs (Bashirulla et al 1999, Tandros et al 2003, 2007, Ferg et al 2007, Shiokawa et al 2008, Tandros & Lipshitz 2009). Therefore, the data presented in this paper may reflect an involvement of RU486 in destabilizing of some components of the zygotic transcriptome.…”

Maternally-preset program of apoptosis and caspases involved in execution of the apoptosis at midblastula transition (MBT) but not before in <i>Xenopus laevis</i> embryogenesis

“…Caspase-8 mRNA is not a maternal mRNA, but is newly synthesized during cleavage stage (pre-MBT stage) as a result of the overexpression of SAMDC, but not of p53. Based on the results, we conclude that Xenopus embryos have at least two pathways to execute the maternal program of apoptosis; one executed by SAMDC-overexpression, and the other executed by p53-overexpression, and while the former is executed through activation of caspase-8 before the activation of caspase-9, the latter is activated not through caspase-8 but directly through caspase-9 [88] (Figure 20). We assume that further experiment to clarify the control mechanism of these unique apoptotic systems in Xenopus early embryos would provide important insights not only for the studies of apoptosis itself but also for the elucidation of the developmental control mechanism.…”

“…From Shiokawa et al[87].OPEN ACCESS A model which shows sequence of events in activetion of apoptosis in SAMDC-and p53-overexpressed Xenopus embryos. From Shiokawa et al[88].…”