Evidence map›Paper›PMID 25468951›Full record

ArticleDisease models & mechanisms2015

Impact of retinoic acid exposure on midfacial shape variation and manifestation of holoprosencephaly in Twsg1 mutant mice.

Charles J Billington, Brian Schmidt, Ralph S Marcucio, Benedikt Hallgrimsson, Rajaram Gopalakrishnan, Anna Petryk

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Disease models & mechanisms, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.9field-weighted citation impact, top 26% 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, 18 citations in OpenAlex.

  1. Article
  2. Article
  3. Multifaceted Functions of TWSG1: From Embryogenesis to Cancer Development.International journal of molecular sciences · 2022
    Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Nongenetic risk factors for holoprosencephaly: An updated review of the epidemiologic literature.American journal of medical genetics. Part C, Seminars in medical genetics · 2018
    Review
  9. Six3 dosage mediates the pathogenesis of holoprosencephaly.Development (Cambridge, England) · 2016
    Article
  10. Molecular mechanisms of midfacial developmental defects.Developmental dynamics : an official publication of the American Association of Anatomists · 2016
    Review
  11. Morphometrics, 3D Imaging, and Craniofacial Development.Current topics in developmental biology · 2015
    Review
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

6 authors at 3 institutions in 2 countries.

Charles J BillingtonDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55454, USA. Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55454, USA.
Brian SchmidtDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55454, USA.
Ralph S MarcucioDepartment of Orthopedic Surgery, University of California, San Francisco, CA 94110, USA.
Benedikt HallgrimssonDepartment of Cell Biology & Anatomy, University of Calgary, Calgary, AB T2N 4N1, Canada.
Rajaram GopalakrishnanDiagnostic/Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN 55455, USA.
Anna PetrykDepartment of Pediatrics, University of Minnesota, Minneapolis, MN 55454, USA. Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55454, USA. petry005@umn.edu.
University of Minnesota · USUniversity of Calgary · CAUniversity of California, San Francisco · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM008244 · NIGMS · UNIVERSITY OF MINNESOTA TWIN CITIES · PI SHIMIZU, YOJI · 1988 to 2024
$13.6M
The role of continuous phenotypic variation in structural defects of the faceR01DE019638 · NIDCR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Benedikt Hallgrimsson, Ralph S Marcucio · 2010 to 2026
$7.3M
Developmental mechanisms underlying genotype-phenotype correlationsR01DE021708 · NIDCR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HALLGRIMSSON, BENEDIKT, MARCUCIO, RALPH S · 2011 to 2015
$1.9M
TWISTED GASTRULATION AND MANDIBULAR ARCH MORPHOGENESISR01DE016601 · NIDCR · UNIVERSITY OF MINNESOTA · PI PETRYK, ANNA · 2007 to 2011
$1.8M
Minnesota Craniofacial Research Training ProgramR90DE023058 · NIDCR · UNIVERSITY OF MINNESOTA · PI MANSKY, KIM CARPENTER · 2012 to 2022
$1.2M
Prevention of HPE in a mouse model susceptible to retinoic acid teratogenicityR56DE023530 · NIDCR · UNIVERSITY OF MINNESOTA · PI PETRYK, ANNA · 2013 to 2013
$114k
NIDCR NIH HHS R01 DE016601NIDCR NIH HHS R01 DE019638NIDCR NIH HHS R01 DE021708NIDCR NIH HHS R56 DE023530NIDCR NIH HHS R90 DE023058NIGMS NIH HHS T32 GM008244
6 · The paper itself

Abstract

Holoprosencephaly (HPE) is a developmental anomaly characterized by inadequate or absent midline division of the embryonic forebrain and midline facial defects. It is believed that interactions between genes and the environment play a role in the widely variable penetrance and expressivity of HPE, although direct investigation of such effects has been limited. The goal of this study was to examine whether mice carrying a mutation in a gene encoding the bone morphogenetic protein (BMP) antagonist twisted gastrulation (Twsg1), which is associated with a low penetrance of HPE, are sensitized to retinoic acid (RA) teratogenesis. Pregnant Twsg1(+/-) dams were treated by gavage with a low dose of all-trans RA (3.75 mg/kg of body weight). Embryos were analyzed between embryonic day (E)9.5 and E11.5 by microscopy and geometric morphometric analysis by micro-computed tomography. P19 embryonal carcinoma cells were used to examine potential mechanisms mediating the combined effects of increased BMP and retinoid signaling. Although only 7% of wild-type embryos exposed to RA showed overt HPE or neural tube defects (NTDs), 100% of Twsg1(-/-) mutants exposed to RA manifested severe HPE compared to 17% without RA. Remarkably, up to 30% of Twsg1(+/-) mutants also showed HPE (23%) or NTDs (7%). The majority of shape variation among Twsg1(+/-) mutants was associated with narrowing of the midface. In P19 cells, RA induced the expression of Bmp2, acted in concert with BMP2 to increase p53 expression, caspase activation and oxidative stress. This study provides direct evidence for modifying effects of the environment in a genetic mouse model carrying a predisposing mutation for HPE in the Twsg1 gene. Further study of the mechanisms underlying these gene-environment interactions in vivo will contribute to better understanding of the pathogenesis of birth defects and present an opportunity to explore potential preventive interventions.

Indexed as

AnimalsBone Morphogenetic Protein 2Caspase 3Caspase 7Embryo, MammalianEnzyme ActivationFaceFemaleGene Expression Regulation, DevelopmentalHoloprosencephalyMice, Inbred C57BLMutationNeural Tube DefectsOxidative StressPregnancyProteinsBone Morphogenetic Protein 2Caspase 3Caspase 7ProteinsTretinoinTumor Suppressor Protein p53twisted gastrulation protein, mouseApoptosisBone morphogenetic proteinHoloprosencephalyOxidative stressRetinoic acidTwisted gastrulationTwsg1

Identifiers

PMID25468951
PMCPMC4314779
OpenAlexW2137677119

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Registered trials

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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.