Guillemot F, Nagy A, Auerbach A, Rossant J, Joyner A L
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Nature. 1994 Sep 22;371(6495):333-6. doi: 10.1038/371333a0.
The outer layer of the blastocyst, or trophectoderm, is the first cell lineage to differentiate in the mouse embryo, 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 fulfils the criteria for such a factor. Mash-2 is a mammalian member of the achaete-scute family which encodes basic-helix-loop-helix transcription factors 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-/- 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. Mash-2-/- embryos developed normally and adult Mash-2-/- 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.
胚泡的外层，即滋养外胚层，是小鼠胚胎中第一个分化的细胞谱系，但对其发育的基因控制却知之甚少。谱系特异性转录因子可能在谱系特化中起重要作用，而Mash-2基因的产物符合此类因子的标准。Mash-2是achaete-scute家族的哺乳动物成员，该家族编码碱性螺旋-环-螺旋转录因子，并在胚外滋养层谱系中强烈表达。在植入前发育过程中，Mash-2转录本在雌性生殖系和胚胎中均有发现，但仅在胚外胎盘锥、绒毛膜及其在胎盘中的衍生物中高表达。在植入后任何阶段的初级和次级巨细胞、卵黄囊或尿囊中均未发现Mash-2转录本，并且在原肠胚形成期间，Mash-2转录本仅在胚胎中短暂且低水平存在。为了分析Mash-2在发育中的作用，我们利用基因打靶技术培育出了没有Mash-2功能的小鼠。我们在此报告，Mash-2基因敲除胚胎在交配后10天因胎盘功能衰竭而死亡。在突变胎盘中，海绵滋养层细胞及其前体缺失，绒毛膜外胚层减少。我们通过用几乎完全贡献于胚外组织的四倍体野生型胚胎构建嵌合体，挽救了这种胎盘突变表型。Mash-2基因敲除胚胎发育正常，成年Mash-2基因敲除小鼠也能存活，这表明Mash-2在胚胎本身中没有主要作用。Mash-2是第一个被证明在哺乳动物滋养层谱系发育中起关键作用的转录因子。
