ESSENTIAL ROLE OF MASH-2 IN EXTRAEMBRYONIC DEVELOPMENT
ESSENTIAL ROLE OF MASH-2 IN EXTRAEMBRYONIC DEVELOPMENT
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DOI：
10.1038/371333a0
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发表时间：
1994-09-22
期刊：
影响因子：
64.8
通讯作者：
JOYNER, AL
中科院分区：
文献类型：
--
作者：
GUILLEMOT, F;NAGY, A;JOYNER, AL
胚泡的外层，或称滋养外胚层，是小鼠胚胎中最先分化的细胞谱系（1，2），但对其发育的遗传控制知之甚少。谱系特异性转录因子在谱系特化中可能很重要，Mash-2基因的产物（3，4）满足了此类因子的标准。Mash-2是无毛鳞片家族（5-7）的哺乳动物成员，其编码碱性螺旋环螺旋转录因子（8）并且在胚外滋养层谱系中强烈表达。Mash-2转录本在雌性生殖系和整个植入前发育的胚胎中发现，但后来仅在胎盘中的外胎盘锥、绒毛膜及其衍生物中高度表达。Mash-2转录本在任何着床后阶段的初级和次级巨细胞、卵黄囊或尿囊中均未发现，并且仅在原肠胚形成期间短暂且低水平地存在于胚胎中。为了分析Mash-2在发育中的作用，我们使用基因靶向来产生没有Mash-2功能的小鼠。我们在这里报告，Mash-2（-1-）胚胎在妊娠后10天死于胎盘衰竭。在突变型胎盘中，海绵滋养层细胞及其前体细胞缺失，绒毛膜外胚层减少。我们通过用几乎只对胚外组织有贡献的四倍体野生型胚胎构建嵌合体来拯救这种胎盘突变表型（9，10）。Mash-2（-1-）胚胎发育正常，成年Mash-2（-1-）小鼠存活，表明Mash-2在胚胎本身中没有主要作用。Mash-2是第一个在哺乳动物滋养层细胞谱系发育中起关键作用的转录因子。
THE outer layer of the blastocyst, or trophectoderm, is the first cell lineage to differentiate in the mouse embryo(1,2), but little is known about the genetic control of its development. Lineage-specific transcription factors may be important in lineage specification, and the product of the Mash-2 gene(3,4) fulfils the criteria for such a factor. Mash-2 is a mammalian member of the achaete-scute family(5-7) which encodes basic-helix-loop-helix transcription factors(8) and is strongly expressed in the extraembryonic trophoblast lineage. Mash-2 transcripts are found in the female germ line and in the embryo throughout preimplantation development, but are highly expressed later only in the ectoplacental cone, the chorion and their derivatives in the placenta. Mash-2 transcripts are not found in primary and secondary giant cells, yolk sac or allantois at any post-implantation stage, and are present only transiently and at low levels in the embryo during gastrulation. To analyse the role of Mash-2 in development, we have used gene targeting to generate mice having no Mash-2 function. We report here that Mash-2(-1-) embryos die from placental failure at 10 days postcoitum. In mutant placentas, spongiotrophoblast cells and their precursors are absent and chorionic ectoderm is reduced. We have rescued this placental mutant phenotype by constructing chimaeras with tetraploid wild-type embryos which contribute almost exclusively to extraembryonic tissues(9,10). Mash-2(-1-) embryos developed normally and adult Mash-2(-1-) mice were viable, demonstrating that Mash-2 has no major role in the embryo itself. Mash-2 is the first transcription factor shown to play a critical part in the development of the mammalian trophoblast lineage.