Notch2 is essential for labyrinthine development in the mouse placenta

Notch基因家族编码大跨膜受体，其是进化上保守的细胞间信号传导机制的组分。小鼠Notch 2的锚蛋白重复序列的突变导致胚胎11.5天（E11.5）的胚胎死亡，表明Notch 2在小鼠的植入后发育中起重要作用。在全胚培养中的突变胚胎发育表明，致死性可能是由额外胚胎组织的缺陷引起的。组织学检查和原位杂交分析显示，在迷宫层的突变胎盘血管发生明显正常分化的次级巨细胞和海绵滋养层细胞不足。通过用四倍体（4 N）野生型胚胎产生嵌合概念用途来延迟致死性。这些结果共同表明，Notch 2突变体的致命缺陷是在胎盘滋养层细胞。然而，突变细胞对E12.5嵌合胎盘的所有层都有贡献，表明突变不影响细胞命运决定或滋养层亚型的存活。相反，它损害了胚胎滋养层细胞的生理功能，可能包括与尿囊间充质的细胞-细胞相互作用。此外，4 N拯救的突变胚胎不能存活超过E12.5，此时它们表现出贫血表型和脐带发育不足。因此，Notch 2不是胚胎滋养层和尿囊中胚层细胞的早期细胞命运决定所需的细胞自主，但在功能性迷路层和脐带的进一步形成中起着不可或缺的作用。

The Notch gene family encodes large Tran membrane receptors that are components of an evolutionarily conserved intercellular signaling mechanism. Mutation in the ankyrin repeats of mouse Notch2 results in embryonic lethality by embryonic day 11.5 (E11.5), indicating that Notch2 plays an essential role in post implantation development in mice. Development of the mutant embryos in whole embryo culture indicated that the lethality was likely caused by defects in the extra embryonic tissues. Histological examination and in situ hybridization analysis revealed inadequate vasculogenesis in the labyrinth layer of the mutant placenta with apparently normal differentiation of secondary giant cells and spongiotrophoblast cells. The lethality was delayed by production of chimeric concept uses with tetraploid (4N) wild type embryos. These results collectively suggest that the fatal defect in Notch2 mutants is in labyrinthine trophoblast cells. Mutant cells, however, contributed to all layers of E12.5 chimeric placentas, indicating that the mutation did not affect the cell fate decision or the survival of trophoblast subtypes. Rather, it compromised physiological functions of labyrinthine trophoblast cells, probably including cell-cell interactions with allantoic mesenchyme. Furthermore, the 4N-rescued mutant embryos did not survive beyond E12.5, at which time they exhibited an anemic phenotype and insufficient development of the umbilical cord. Thus, Notch2 is not cell autonomously required for the early cell fate determination of labyrinthine trophoblast and allantoic mesodermal cells, but plays an indispensable role in the further formation of a functional labyrinth layer and the umbilical cord.