Kruger Robin E, Frum Tristan, Brumm A Sophie, Hickey Stephanie L, Niakan Kathy K, Aziz Farina, Shammami Marcelio A, Roberts Jada G, Ralston Amy
Cell and Molecular Biology Ph.D. Program, Michigan State University, East Lansing, MI, 48824, USA.
Reproductive and Developmental Sciences Training Program, Michigan State University, East Lansing, MI, 48824, USA.
bioRxiv. 2024 Jan 24:2024.01.23.576717. doi: 10.1101/2024.01.23.576717.
Bone Morphogenic Protein (BMP) signaling plays an essential and highly conserved role in axial patterning in embryos of many externally developing animal species. However, in mammalian embryos, which develop inside the mother, early development includes an additional stage known as preimplantation. During preimplantation, the epiblast lineage is segregated from the extraembryonic lineages that enable implantation and development . Yet, the requirement for BMP signaling in mouse preimplantation is imprecisely defined. We show that, in contrast to prior reports, BMP signaling (as reported by SMAD1/5/9 phosphorylation) is not detectable until implantation, when it is detected in the primitive endoderm - an extraembryonic lineage. Moreover, preimplantation development appears normal following deletion of maternal and zygotic an essential effector of BMP signaling. In fact, mice lacking maternal are viable. Finally, we uncover a new requirement for zygotic in epiblast scaling and cavitation immediately after implantation, via a mechanism involving FGFR/ERK attenuation. Altogether, our results demonstrate no role for BMP4/SMAD4 in the first lineage decisions during mouse development. Rather, multi-pathway signaling among embryonic and extraembryonic cell types drives epiblast morphogenesis post-implantation.
骨形态发生蛋白（BMP）信号传导在许多体外发育动物物种胚胎的轴向模式形成中起着至关重要且高度保守的作用。然而，在母体内发育的哺乳动物胚胎中，早期发育包括一个额外的阶段，即着床前阶段。在着床前阶段，上胚层谱系与能够实现着床和发育的胚外谱系分离。然而，小鼠着床前阶段对BMP信号传导的需求尚不清楚。我们发现，与先前的报道相反，BMP信号传导（通过SMAD1/5/9磷酸化来检测）直到着床时才被检测到，此时在原始内胚层（一种胚外谱系）中被检测到。此外，在缺失母源和合子源的BMP信号传导关键效应因子后，着床前发育似乎正常。事实上，缺乏母源该因子的小鼠是可存活的。最后，我们发现合子源该因子在着床后通过一种涉及FGFR/ERK减弱的机制，在上胚层扩展和空化过程中有新的需求。总之，我们的结果表明BMP4/SMAD4在小鼠发育的第一个谱系决定中没有作用。相反，胚胎和胚外细胞类型之间的多途径信号传导驱动着床后上胚层形态发生。
