Evidence map›Paper›PMID 41619969›Full record

ArticleCellular and molecular gastroenterology and hepatology2026

Protocadherin 20 Is a POU Class 2 Homeobox 3 Target Gene Required for Proper Tuft Cell Microvillus Organization.

Katherine E Ankenbauer, Yilin Yang, Chi-Yeh Chung, Leonardo R Andrade, Sammy Weiser Novak, Brenda Jarvis, Wahida H Ali Hanel, Jiayue Liu, Victoria Sarkisian, Neil Dani and 10 more

Abstract read
In one paragraph

Article in Cellular and molecular gastroenterology and hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors.

Katherine E AnkenbauerDepartment of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, Tennessee.
Yilin YangDepartment of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Computational Systems Biology, Vanderbilt University, Nashville, Tennessee.
Chi-Yeh ChungGene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California.
Leonardo R AndradeLaboratory of Genetics and Center for Chemical Biology and Proteomics, The Salk Institute for Biological Studies, La Jolla, California.
Sammy Weiser NovakWaitt Advanced Biophotonics Center, Salk Institute for Biological Studies, La Jolla, California.
Brenda JarvisDepartment of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee.
Wahida H Ali HanelGene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California; Biological and Physical Sciences Department, Columbus State Community College, Columbus, Ohio.
Jiayue LiuDepartment of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee.
Victoria SarkisianDepartment of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee.
Neil DaniDepartment of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee.
Evan KrystofiakDepartment of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee.
Gaizun HuDepartment of Molecular Physiology and Biological Physics, Center for Membrane and Cell Physiology, University of Virginia School of Medicine, Charlottesville, Virginia.
Seham EbrahimDepartment of Molecular Physiology and Biological Physics, Center for Membrane and Cell Physiology, University of Virginia School of Medicine, Charlottesville, Virginia.
Bechara KacharLaboratory of Cell Structure and Dynamics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland.
Qizhi GongDepartment of Cell Biology and Human Anatomy, School of Medicine, University of California, Davis, California.
Geoffrey M WahlGene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California.
Ken S LauDepartment of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Computational Systems Biology, Vanderbilt University, Nashville, Tennessee; Chemical and Physical Biology Program, Vanderbilt University, Nashville, Tennessee; Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee; Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee; Vanderbilt Digestive Disease Research Center, Vanderbilt University Medical Center, Nashville, Tennessee.
Jeffrey W BrownDivision of Gastroenterology, Department of Medicine, Washington University in St. Louis, Missouri.
Uri ManorDepartment of Cell and Developmental Biology, University of California, San Diego, California.
Kathleen E DelGiornoDepartment of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee; Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Computational Systems Biology, Vanderbilt University, Nashville, Tennessee; Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee; Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee; Vanderbilt Digestive Disease Research Center, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address: kathleen.delgiorno@vanderbilt.edu.

Funding

Vanderbilt-Ingram Cancer Center SPORE in Gastrointestinal CancerP50CA236733 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI STEPHEN W. FESIK · 2019 to 2026
$19.6M
MOLECULAR BASIS OF TRANSDUCTION IN AUDITORY SENSORY ORGANSZ01DC000002 · NIDCD · NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS · PI KACHAR, BECHARA · 1989 to 2008
$3.9M
A multi-modality approach to decode epithelial heterogeneity and function in metaplasiaR35GM142709 · NIGMS · VANDERBILT UNIVERSITY · PI DELGIORNO, KATHLEEN ELIZABETH · 2021 to 2025
$2.0M
Conventional 200 keV Transmission Electron MicroscopeS10OD034315 · OD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI JEROME, WALTER G · 2023 to 2023
$597k
Intramural NIH HHS Z01 DC000002NCI NIH HHS P50 CA236733NIGMS NIH HHS R35 GM142709NIH HHS S10 OD034315
6 · The paper itself

Abstract

BACKGROUND &

aimsTuft cells play protective roles in infection, inflammation, and tumorigenesis through the secretion of cytokines and eicosanoids. Tuft cells are known for their tall, blunt microvilli, thought to be analogous to mechanosensory hair cell stereocilia; however, a functional role for the microvillar apparatus has not been identified. POU Class 2 Homeobox 3 (POU2F3) is the master regulator transcription factor for tuft cells, yet how POU2F3 drives formation of this unique structure is unknown. Here, we aimed to identify POU2F3 target genes and commonalities between tuft and hair cells to better understand this unique structure.

methodsPOU2F3 chromatin immunoprecipitation sequencing was performed on tuft cells and compared with the hair cell transcriptome. Tuft cell RNA sequencing datasets were interrogated for hair cell structural and mechanosensory genes; expression was validated. Intestinal and gallbladder tuft cells were examined using multiple light and electron microscopy modalities. Protocadherin 20 (PCDH20) was knocked down in mouse models, and ultrastructural analyses were performed. The tuft cell cytoskeleton was modeled using AlphaFold3 prediction.

resultsGenes encoding structural and mechanosensory proteins common to both tuft and hair cells, including Pcdh20, were identified. Imaging localized PCDH20 to tuft cell microvilli and hair cell stereocilia. Genetic ablation of Pcdh20 in mice resulted in structural defects in tuft cell microvilli, including loss of rigidity and organization. Molecular modeling suggests PCDH20 homodimers link adjacent microvilli.

conclusionsPcdh20 is a POU2F3 target gene in tuft cells, critical to maintain the rigid microvillar apparatus. These findings, together with the shared expression of mechanosensory components like transmembrane channel-like protein 1, support the hypothesis that tuft cells could have mechanosensory capabilities analogous to cochlear hair cells.

Indexed as

CadherinsMicrovilliOctamer Transcription FactorsTuft CellsAnimalsMiceCadherinsOctamer Transcription FactorsChIP-seqHair CellsMechanotransductionStereocilia

Identifiers

PMID41619969
PMCPMC13051935

What OpenQuestion holds

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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.