Evidence map›Paper›PMID 36218393›Full record

ArticleGenetics2022

Conserved roles for Hnf4 family transcription factors in zebrafish development and intestinal function.

Jennifer K Heppert, Colin R Lickwar, Matthew C Tillman, Briana R Davis, James M Davison, Hsiu-Yi Lu, Wei Chen, Elisabeth M Busch-Nentwich, David L Corcoran, John F Rawls

Open access · bronzeAbstract read
In one paragraph

Article in Genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

7 citing papers in PubMed, 16 citations in OpenAlex.

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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

10 authors at 3 institutions in 2 countries.

Jennifer K HeppertDepartment of Molecular Genetics and Microbiology, Duke Microbiome Center, Duke University School of Medicine, Durham, NC 27710, USA.ORCID 0000-0001-8602-414X
Colin R LickwarDepartment of Molecular Genetics and Microbiology, Duke Microbiome Center, Duke University School of Medicine, Durham, NC 27710, USA.ORCID 0000-0002-7312-6291
Matthew C TillmanDepartment of Molecular Genetics and Microbiology, Duke Microbiome Center, Duke University School of Medicine, Durham, NC 27710, USA.ORCID 0000-0001-8516-751X
Briana R DavisDepartment of Molecular Genetics and Microbiology, Duke Microbiome Center, Duke University School of Medicine, Durham, NC 27710, USA.ORCID 0000-0003-0109-7441
James M DavisonDepartment of Molecular Genetics and Microbiology, Duke Microbiome Center, Duke University School of Medicine, Durham, NC 27710, USA.ORCID 0000-0003-2453-7227
Hsiu-Yi LuDepartment of Molecular Genetics and Microbiology, Duke Microbiome Center, Duke University School of Medicine, Durham, NC 27710, USA.ORCID 0000-0002-8539-1690
Wei ChenCenter for Genomics and Computational Biology, Duke University School of Medicine, Durham, NC 27710, USA.
Elisabeth M Busch-NentwichSchool of Biological and Behavioural Sciences, Queen Mary University of London, E1 4NS London, UK.ORCID 0000-0001-6450-744X
David L CorcoranCenter for Genomics and Computational Biology, Duke University School of Medicine, Durham, NC 27710, USA.ORCID 0000-0001-7460-9247
John F RawlsDepartment of Molecular Genetics and Microbiology, Duke Microbiome Center, Duke University School of Medicine, Durham, NC 27710, USA.ORCID 0000-0002-5976-5206
Duke University · USQueen Mary University of London · GBUniversity of North Carolina at Chapel Hill · US

Funding

Role of IL-10 in APC Regulation of Protective vs. Pathogenic T Cell Responses toP01DK094779 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SARTOR, RYAN B · 2013 to 2023
$17.9M
GASTROENTEROLOGY RESEARCH TRAININGT32DK007737 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SHEHZAD Z. SHEIKH · 1996 to 2026
$7.8M
Identifying genes required for digestive physiology and lipid metabolismR01DK093399 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI STEVEN A FARBER, John F Rawls · 2013 to 2026
$7.6M
Microbial regulation of intestinal lipid metabolism and its physiological consequencesR01DK131742 · NIDDK · DUKE UNIVERSITY · PI RAWLS, JOHN F, YEN, CHI- LIANG ERIC · 2022 to 2025
$2.6M
NIDDK NIH HHS P01 DK094779NIDDK NIH HHS R01 DK093399NIDDK NIH HHS R01 DK131742NIDDK NIH HHS T32 DK007737
6 · The paper itself

Abstract

Transcription factors play important roles in the development of the intestinal epithelium and its ability to respond to endocrine, nutritional, and microbial signals. Hepatocyte nuclear factor 4 family nuclear receptors are liganded transcription factors that are critical for the development and function of multiple digestive organs in vertebrates, including the intestinal epithelium. Zebrafish have 3 hepatocyte nuclear factor 4 homologs, of which, hnf4a was previously shown to mediate intestinal responses to microbiota in zebrafish larvae. To discern the functions of other hepatocyte nuclear factor 4 family members in zebrafish development and intestinal function, we created and characterized mutations in hnf4g and hnf4b. We addressed the possibility of genetic redundancy amongst these factors by creating double and triple mutants which showed different rates of survival, including apparent early lethality in hnf4a; hnf4b double mutants and triple mutants. RNA sequencing performed on digestive tracts from single and double mutant larvae revealed extensive changes in intestinal gene expression in hnf4a mutants that were amplified in hnf4a; hnf4g mutants, but limited in hnf4g mutants. Changes in hnf4a and hnf4a; hnf4g mutants were reminiscent of those seen in mice including decreased expression of genes involved in intestinal function and increased expression of cell proliferation genes, and were validated using transgenic reporters and EdU labeling in the intestinal epithelium. Gnotobiotics combined with RNA sequencing also showed hnf4g has subtler roles than hnf4a in host responses to microbiota. Overall, phenotypic changes in hnf4a single mutants were strongly enhanced in hnf4a; hnf4g double mutants, suggesting a conserved partial genetic redundancy between hnf4a and hnf4g in the vertebrate intestine.

Indexed as

Hepatocyte Nuclear Factor 4Intestinal MucosaZebrafishZebrafish ProteinsAnimalsIntestinesHepatocyte Nuclear Factor 4Zebrafish ProteinsHNF4host–microbe interactionintestinemicrobiotaNR2Anuclear receptortranscription factorzebrafish development

Identifiers

PMID36218393
PMCPMC9713462
OpenAlexW4304191633

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.