Evidence map›Paper›PMID 38752427›Full record

ArticleDevelopment (Cambridge, England)2024

Smad4 is essential for epiblast scaling and morphogenesis after implantation, but nonessential before implantation.

Robin E Kruger, Tristan Frum, A Sophie Brumm, Stephanie L Hickey, Kathy K Niakan, Farina Aziz, Marcelio A Shammami, Jada G Roberts, Amy Ralston

Abstract read
In one paragraph

Article in Development (Cambridge, England), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Molecular basis of competence for neural induction in the chick embryo.bioRxiv : the preprint server for biology · 2026
    Article
  2. Article
  3. Article
4 · The record

Corrections and comments

  • Update of
    2024
5 · Who and what money

Authors and funding

9 authors.

Robin E KrugerCell and Molecular Biology Ph.D. Program, Michigan State University, East Lansing, MI 48824, USA.ORCID 0000-0002-2190-2455
Tristan FrumDepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA.ORCID 0000-0003-3452-8762
A Sophie BrummHuman Embryo and Stem Cell Laboratory, The Francis Crick Institute,London NW1 1AT, UK.ORCID 0000-0001-8371-847X
Stephanie L HickeyResearch Technology Support Facility, Michigan State University, East Lansing, MI 48824, USA.ORCID 0000-0002-9768-786X
Kathy K NiakanHuman Embryo and Stem Cell Laboratory, The Francis Crick Institute,London NW1 1AT, UK.ORCID 0000-0003-1646-4734
Farina AzizCell and Molecular Biology Ph.D. Program, Michigan State University, East Lansing, MI 48824, USA.ORCID 0000-0002-0597-3552
Marcelio A ShammamiReproductive and Developmental Sciences Training Program, Michigan State University, East Lansing, MI 48824, USA.ORCID 0000-0002-1095-8146
Jada G RobertsMolecular, Cellular, and Integrative Physiology Ph.D. Program, Michigan State University, East Lansing, MI 48824, USA.ORCID 0000-0001-5733-5416
Amy RalstonDepartment of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA.ORCID 0000-0003-3755-8262

Funding

Molecular mechanisms regulating formation of diverse stem cell progenitorsR35GM131759 · NIGMS · MICHIGAN STATE UNIVERSITY · PI Amy Ralston · 2019 to 2026
$3.0M
Reproductive and Developmental Sciences Training Program - T32T32HD087166 · NICHD · MICHIGAN STATE UNIVERSITY · PI Ronald L Chandler, Keith E Latham · 2016 to 2026
$2.5M
Michigan State UniversityNICHD NIH HHS T32 HD087166NIGMS NIH HHS R35 GM131759NIH HHS T32 HD087166Wellcome Trust 221856/Z/20/ZWellcome Trust FC001120
6 · The paper itself

Abstract

Bone morphogenic protein (BMP) signaling plays an essential and highly conserved role in embryo axial patterning in animal species. However, in mammalian embryos, which develop inside the mother, early development includes a preimplantation stage, which does not occur in externally developing embryos. During preimplantation, the epiblast is segregated from extra-embryonic lineages that enable implantation and development in utero. Yet, the requirement for BMP signaling is imprecisely defined in mouse early embryos. Here, we show that, in contrast to previous reports, BMP signaling (SMAD1/5/9 phosphorylation) is not detectable until implantation when it is detected in the primitive endoderm - an extra-embryonic lineage. Moreover, preimplantation development appears to be normal following deletion of maternal and zygotic Smad4, an essential effector of canonical 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 extra-embryonic cell types drives epiblast morphogenesis postimplantation.

Indexed as

Embryo ImplantationGerm LayersMorphogenesisSmad4 ProteinAnimalsBlastocystBone Morphogenetic Protein 4Embryo, MammalianEmbryonic DevelopmentEndodermFemaleGene Expression Regulation, DevelopmentalMiceMice, KnockoutSignal TransductionBmp4 protein, mouseBone Morphogenetic Protein 4Smad4 ProteinSmad4 protein, mouseEpiblastExtra-embryonicMaternal and zygotic gene deletionMorphogenesisMousePSMAD1/5/9

Identifiers

PMID38752427
PMCPMC11190579

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.