Epiblast fragmentation by shedding—a novel mechanism to eliminate cells in post-implantation mouse embryos

Halimi, Rivi; Levin-Zaidman, Smadar; Levin-Salomon, Vered; Bialik, Shani; Kimchi, Adi

doi:10.1038/s41418-021-00918-5

Cited by 1 publication

(1 citation statement)

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“…Our data suggest that ectopic upregulation of pERK resulting from loss of Smad4 is detrimental to epiblast cavitation; however, the mechanisms of how these two pathways interact with one another and regulate cavitation remain unclear. SMAD4 could regulate several processes associated with epiblast cavitation, including epiblast cell apoptosis or epiblast cell polarization and lumenogenesis (Bedzhov and Zernicka-Goetz, 2014; Coucouvanis and Martin, 1995; Coucouvanis and Martin, 1999; Halimi et al, 2022) (Fig 5B-C). Alternatively, SMAD4 could promote epiblast maturation, defined here as the transition from a naïve to primed state which normally occurs in epiblast cells between preimplantation and post-implantation stages (Boroviak et al, 2015; Nichols and Smith, 2009).…”

Section: Discussionmentioning

confidence: 99%

Smad4is essential for epiblast scaling and morphogenesis after implantation, but nonessential prior to implantation in the mouse

Kruger,

Frum,

Brumm

et al. 2024

Preprint

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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 in utero. 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 Smad4, an essential effector of BMP signaling. In fact, mice lacking maternal Smad4 are viable. Finally, we uncover a new requirement for zygotic Smad4 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.

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