Evidence map›Paper›PMID 27924807›Full record

ArticleEuropean journal of human genetics : EJHG2017

Genetic and Molecular Analyses indicate independent effects of TGIFs on Nodal and Gli3 in neural tube patterning.

Kenichiro Taniguchi, Anoush E Anderson, Tiffany A Melhuish, Anne L Carlton, Arkadi Manukyan, Ann E Sutherland, David Wotton

Open access · bronzeAbstract read
In one paragraph

Article in European journal of human genetics : EJHG, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 12% of its field
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

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Modeling the complex etiology of holoprosencephaly in mice.American journal of medical genetics. Part C, Seminars in medical genetics · 2018
    Review
  8. Functions of TGIF homeodomain proteins and their roles in normal brain development and holoprosencephaly.American journal of medical genetics. Part C, Seminars in medical genetics · 2018
    Article
  9. Article
  10. Article
  11. LncRNA Expression in CD4+ T Cells in Neurosyphilis Patients.Frontiers in cellular and infection microbiology · 2017
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Kenichiro TaniguchiDepartment of Biochemistry and Molecular Genetics, and Center for Cell Signaling, University of Virginia, Charlottesville, VA, USA.
Anoush E AndersonDepartment of Biochemistry and Molecular Genetics, and Center for Cell Signaling, University of Virginia, Charlottesville, VA, USA.
Tiffany A MelhuishDepartment of Biochemistry and Molecular Genetics, and Center for Cell Signaling, University of Virginia, Charlottesville, VA, USA.
Anne L CarltonDepartment of Biochemistry and Molecular Genetics, and Center for Cell Signaling, University of Virginia, Charlottesville, VA, USA.
Arkadi ManukyanDepartment of Biochemistry and Molecular Genetics, and Center for Cell Signaling, University of Virginia, Charlottesville, VA, USA.
Ann E SutherlandDepartment of Cell Biology, University of Virginia, Charlottesville, VA, USA.
David WottonDepartment of Biochemistry and Molecular Genetics, and Center for Cell Signaling, University of Virginia, Charlottesville, VA, USA.
University of Virginia · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007267 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI GARCIA-BLANCO, MARIANO A. · 1985 to 2024
$13.4M
TRAINING IN CELL AND MOLECULAR BIOLOGYT32GM008136 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI STUKENBERG, P. TODD · 1985 to 2020
$8.5M
TRAINING IN THE PHARMACOLOGICAL SCIENCEST32GM007055 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI LYNCH, KEVIN R. · 1985 to 2022
$7.2M
Regulation of neural development by TGF beta family signalingR01NS077958 · NINDS · UNIVERSITY OF VIRGINIA · PI WOTTON, DAVID · 2012 to 2016
$1.7M
Regulation of Placental and Embryonic Development by TgifsR01HD052707 · NICHD · UNIVERSITY OF VIRGINIA · PI WOTTON, DAVID · 2007 to 2011
$1.5M
TGF beta regulation of cilium-dependent signalingR01GM099853 · NIGMS · UNIVERSITY OF VIRGINIA · PI WOTTON, DAVID · 2012 to 2015
$1.2M
NICHD NIH HHS R01 HD052707NIGMS NIH HHS R01 GM099853NIGMS NIH HHS T32 GM007055NIGMS NIH HHS T32 GM007267NIGMS NIH HHS T32 GM008136NINDS NIH HHS R01 NS077958
6 · The paper itself

Abstract

Holoprosencephaly (HPE) is a prevalent craniofacial developmental disorder that has both genetic and environmental causes. The gene encoding TG-interacting factor 1 (TGIF1) is among those that are routinely screened in HPE patients. However, the mechanisms by which TGIF1 variants cause HPE are not fully understood. TGIF1 is a transcriptional repressor that limits the output of the Transforming Growth Factor ß (TGFß)/Nodal signaling pathway, and HPE in patients with TGIF1 variants has been suggested to be due to increased Nodal signaling. Mice lacking both Tgif1 and its paralog, Tgif2, have HPE, and embryos lacking Tgif function do not survive past mid-gestation. Here, we show that in the presence of a Nodal heterozygous mutation, proliferation defects are rescued and a proportion of embryos lacking all Tgif function survive to late gestation. However, these embryos have a classic HPE phenotype, suggesting that this is a Nodal-independent effect of Tgif loss of function. Further, we show that the Gli3 gene is a direct target for repression by Tgifs, independent of TGFß/Nodal signaling, consistent with Tgif mutations causing HPE via Nodal-independent effects on the Sonic Hedgehog (Shh) pathway. Based on this work, we propose a model for distinct functions of Tgifs in the Nodal and Shh/Gli3 pathways during forebrain development.

Indexed as

AnimalsCell Line, TumorCells, CulturedHedgehog ProteinsHoloprosencephalyHomeodomain ProteinsHumansKruppel-Like Transcription FactorsMiceMice, Inbred C57BLMutationNerve Tissue ProteinsNeural TubeNodal ProteinRepressor ProteinsSignal TransductionGli3 protein, mouseHedgehog ProteinsHomeodomain ProteinsKruppel-Like Transcription FactorsNerve Tissue ProteinsNodal ProteinNodal protein, mouseRepressor ProteinsShh protein, mouseTgif1 protein, mouseZinc Finger Protein Gli3

Identifiers

PMID27924807
PMCPMC5255961
OpenAlexW2560292764

What OpenQuestion holds

Textmetadata
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.