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 in Xenopus Early Embryogenesis
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 in Xenopus Early Embryogenesis
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MBT 前胚胎中的基因表达和在 MBT 前后执行的母系遗传细胞凋亡程序的激活作为非洲爪蟾早期胚胎发生的故障安全机制
DOI：
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
H. Hara
中科院分区：
文献类型：
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作者：
K. Shiokawa;M. Aso;T. Kondo;Hiroaki Uchiyama;S. Kuroyanagi;Jun;Senji Takahashi;M. Kajitani;C. Kaito;K. Sekimizu;E. Takayama;K. Igarashi;H. Hara
S-腺苷蛋氨酸脱羧酶是一种能将甲基供体S-腺苷甲酮转化为多胺生物合成的氨丙基供体脱羧腺苷蛋氨酸的酶。在对非洲爪哇早期胚胎基因表达调控的研究中，我们克隆了非洲爪哇SAMDC的基因，并将其基因通过显微注射到非洲爪哇受精卵中过表达。在注射了mRNA的胚胎中，SAMDC的水平显著增加，SAM耗尽，蛋白质合成受到极大的抑制，但细胞多胺含量没有明显变化。SAMDC高表达的胚胎在囊胚期发育正常，但在囊胚期或中期囊胚期，所有的胚胎都被解离成细胞，并由于执行细胞凋亡而被破坏。在卵裂过程中，SAMDC过表达的胚胎转录了caspase-8基因，随后caspase-9被激活。当我们在受精卵中过表达P53mRNA时，MBT也发生了类似的凋亡，但在这种情况下，caspase-8没有转录，而caspase-9却被激活了。SAMDC过表达诱导的细胞凋亡可被Bcl2完全抑制，而P53过表达或其他毒性药物治疗只能部分挽救SAMDC过度诱导的细胞凋亡。当我们仅将SAMDC mRNA注入8-32-细胞胚胎的一个卵裂球时，注射了mRNA的卵裂球的后代细胞被分离到囊胚中并在囊胚腔内发生凋亡，尽管这样的胚胎继续发育并成为具有不同程度异常的蝌蚪，反映了被淘汰细胞的发育命运。因此，胚胎细胞似乎在MBT检查自己，如果出现生理上严重损坏的细胞，它们就会通过激活和执行母系遗传的凋亡程序从胚胎中消除。我们认为，在MBT上执行的细胞凋亡是早期发育的一种“故障安全”机制，以保护胚胎免受卵裂过程中发生的意外损害。
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.
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非洲爪蟾原肠胚形成早期发育调节的细胞凋亡激活导致细胞周期间期细胞周期蛋白 A 降解。
DOI：
10.1242/dev.124.16.3185
发表时间：
1997
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Stack,JH;Newport,JW
通讯作者：
Newport,JW
影响因子：
4.6
作者：
D. Kane;C. Kimmel
通讯作者：
D. Kane;C. Kimmel
影响因子：
2.7
作者：
D. Shook;C. Majer;R. Keller
通讯作者：
D. Shook;C. Majer;R. Keller
影响因子：
2.7
作者：
MOODY, SA
通讯作者：
MOODY, SA
对 INCENP 在整个有丝分裂过程中分布的分析揭示了在分裂沟形成的中期和早期事件期间染色体中存在结构变化的途径。
影响因子：
4
作者：
Earnshaw,WC;Cooke,CA
通讯作者：
Cooke,CA