Evidence map›Paper›PMID 25176043›Full record

ArticleDevelopmental biology2014

Identification of Annexin A4 as a hepatopancreas factor involved in liver cell survival.

Danhua Zhang, Vladislav S Golubkov, Wenlong Han, Ricardo G Correa, Ying Zhou, Sunyoung Lee, Alex Y Strongin, P Duc Si Dong

Abstract read
In one paragraph

Article in Developmental biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing 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

43 citing papers in PubMed.

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  4. Exosomes as immunomodulators in autoimmune inflammation: implications for primary Sjögren's disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
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  17. Notch-Sox9 Axis Mediates Hepatocyte Dedifferentiation inInternational journal of molecular sciences · 2022
    Article
  18. Article
  19. Article
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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

8 authors.

Danhua ZhangSanford Children's Health Research Center, Programs in Genetic Disease, Development and Aging, and Stem Cell and Regenerative Biology, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA; Graduate School of Biomedical Sciences, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.
Vladislav S GolubkovInfectious and Inflammatory Disease Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.
Wenlong HanNCI-Designated Cancer Center, Tumor Microenvironment Program, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Ricardo G CorreaInfectious and Inflammatory Disease Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.
Ying ZhouSanford Children's Health Research Center, Programs in Genetic Disease, Development and Aging, and Stem Cell and Regenerative Biology, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA; Graduate School of Biomedical Sciences, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.
Sunyoung LeeNCI-Designated Cancer Center, Tumor Microenvironment Program, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Alex Y StronginInfectious and Inflammatory Disease Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.
P Duc Si DongSanford Children's Health Research Center, Programs in Genetic Disease, Development and Aging, and Stem Cell and Regenerative Biology, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA; Graduate School of Biomedical Sciences, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA. Electronic address: ducdong@sanfordburnham.org.

Funding

Unlocking Regenerative Potential through in Vivo Genetic ReprogrammingDP2DK098092 · NIDDK · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI DONG, P. DUC SI · 2012 to 2012
$2.9M
NIDDK NIH HHS 1DP2DK098092NIDDK NIH HHS DP2 DK098092
6 · The paper itself

Abstract

To gain insight into liver and pancreas development, we investigated the target of 2F11, a monoclonal antibody of unknown antigen, widely used in zebrafish studies for labeling hepatopancreatic ducts. Utilizing mass spectrometry and in vivo assays, we determined the molecular target of 2F11 to be Annexin A4 (Anxa4), a calcium binding protein. We further found that in both zebrafish and mouse endoderm, Anxa4 is broadly expressed in the developing liver and pancreas, and later becomes more restricted to the hepatopancreatic ducts and pancreatic islets, including the insulin producing ß-cells. Although Anxa4 is a known target of several monogenic diabetes genes and its elevated expression is associated with chemoresistance in malignancy, its in vivo role is largely unexplored. Knockdown of Anxa4 in zebrafish leads to elevated expression of caspase 8 and Δ113p53, and liver bud specific activation of Caspase 3 and apoptosis. Mosaic knockdown reveal that Anxa4 is required cell-autonomously in the liver bud for cell survival. This finding is further corroborated with mosaic anxa4 knockout studies using the CRISPR/Cas9 system. Collectively, we identify Anxa4 as a new, evolutionarily conserved hepatopancreatic factor that is required in zebrafish for liver progenitor viability, through inhibition of the extrinsic apoptotic pathway. A role for Anxa4 in cell survival may have implications for the mechanism of diabetic ß-cell apoptosis and cancer cell chemoresistance.

Indexed as

Amino Acid SequenceAnimalsAnimals, Genetically ModifiedAnnexin A4ApoptosisBase SequenceCaspase 3Cell SurvivalEmbryo, NonmammalianGene Expression Regulation, DevelopmentalGene Knockdown TechniquesGreen Fluorescent ProteinsImmunohistochemistryIn Situ HybridizationLiverMicroscopy, ConfocalAnnexin A4Caspase 3Green Fluorescent ProteinsZebrafish Proteins2F11Annexin A4Cell survivalHepatopancreatic ductLiverPancreas

Identifiers

PMID25176043
PMCPMC4229018

What OpenQuestion holds

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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.