Differences in blastomere totipotency in 2-cell mouse embryos are a maternal trait mediated by asymmetric mRNA distribution
Differences in blastomere totipotency in 2-cell mouse embryos are a maternal trait mediated by asymmetric mRNA distribution
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DOI：
10.1093/molehr/gaz051
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发表时间：
2019-11-01
影响因子：
4
通讯作者：
Boiani, M.
中科院分区：
文献类型：
--
作者：
Casser, E.;Wdowik, S.;Boiani, M.
人们普遍认为，哺乳动物胚胎的前两个卵裂球具有同等的全能性，并且这种全能性属于一组调节特性。然而，这种解释忽略了一个重要的方面：证据只来自成功的同卵双胞胎，这只能说明那些能够首先调节的半胚胎对。频繁出现的不完全配对仅仅是一种人工产物，还是它们代表了真正的差异，可能是不完全卵裂球调节生长的能力，或者是任何限制调节的化合物X的分布？利用小鼠胚胎在受精后的2细胞阶段一分为二的模型系统，我们提供了证据，证明母细胞间的差异不受外部因素的调节，并且已经潜伏在卵母细胞中。具体来说，外胚层产生的卵裂球间不平衡在最多样化的培养条件下持续存在，并且在孤雌生殖的对偶中也同样适用。因此，双胞胎囊胚只在一个成员中继续发育的情况分别占合子和孤雌生殖对的65%和57%。细胞间失衡与基因产物的亚细胞分布有关，利用mRNA FISH在超分辨率共聚焦显微镜下记录了上皮细胞相关基因Cops3。Cops3 mRNA的卵裂球分布模式具有α -amanitin抗性。因此，这种不平衡不是源于从头转录，而是源于受精前有效的影响。这些数据揭示了以前未被认识到的2细胞期卵裂球调节能力的限制，并指出了小鼠卵母细胞细胞质组织的各个方面，这些方面在卵裂期间不平等地分离到卵裂球。
It is widely held that the first two blastomeres of mammalian embryos are equally totipotent and that this totipotency belongs to the group of regulative properties. However, this interpretation neglects an important aspect: evidence only came from successful monozygotic twins which can speak only for those pairs of half-embryos that are able to regulate in the first place. Are the frequently occurring incomplete pairs simply an artefact, or do they represent a real difference, be it in the imperfect blastomere's ability to regulate growth or in the distribution of any compound X that constrains regulation? Using the model system of mouse embryos bisected at the 2-cell stage after fertilization, we present evidence that the interblastomere differences evade regulation by external factors and are already latent in oocytes. Specifically, an interblastomere imbalance of epiblast production persists under the most diverse culture conditions and applies to the same extent in parthenogenetic counterparts. As a result, cases in which twin blastocysts continued to develop in only one member account for 65 and 57% of zygotic and parthenogenetic pairs, respectively. The interblastomere imbalance is related to the subcellular distribution of gene products, as documented for the epiblast-related gene Cops3, using mRNA FISH in super-resolution mode confocal microscopy. Blastomere patterns of Cops3 mRNA distribution are alpha-amanitin-resistant. Thus, the imbalance originates not from de novo transcription, but from influences which are effective before fertilisation. These data expose previously unrecognized limits of regulative capacities of 2-cell stage blastomeres and point to aspects of cytoplasmic organization of the mouse oocyte that segregate unequally to blastomeres during cleavage.