Evidence map›Paper›PMID 40627684›Full record

ArticleScience signaling2025

The MDM2-p53 axis regulates norrin/frizzled4 signaling and blood-CNS barrier function.

Jacklyn Levey, Md Abedin, Chi Zhang, Emmanuel Odame, Lingling Zhang, Ha-Neul Jo, Kaia Douglas, Heidi Roehrich, Zhe Chen, Harald J Junge

Abstract read
In one paragraph

Article in Science signaling, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

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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.

Jacklyn LeveyDepartment of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA.ORCID 0000-0002-1358-4047
Md AbedinDepartment of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA.
Chi ZhangDepartment of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.ORCID 0000-0003-2693-6643
Emmanuel OdameDepartment of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA.ORCID 0000-0002-8818-3221
Lingling ZhangDepartment of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA.ORCID 0000-0002-9390-8880
Ha-Neul JoDepartment of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA.ORCID 0000-0002-2602-5754
Kaia DouglasUniversity of Minnesota, Minneapolis, MN 55455, USA.ORCID 0009-0001-2993-7214
Heidi RoehrichDepartment of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA.
Zhe ChenDepartment of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.ORCID 0000-0003-0683-9491
Harald J JungeDepartment of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA.ORCID 0000-0003-2458-6010

Funding

Norrin Signaling in the Retina: Regulation of the Blood-Retina BarrierR01EY024261 · NEI · UNIVERSITY OF MINNESOTA · PI Harald Junge · 2014 to 2026
$4.7M
Investigation of a first-in-class Frizzled4/LRP5 agonist in retinal disease modelsR01EY033316 · NEI · UNIVERSITY OF MINNESOTA · PI Harald Junge · 2022 to 2026
$2.3M
Training Program in Translational Vision SciencesT32EY025187 · NEI · UNIVERSITY OF MINNESOTA · PI Glenn P Lobo, LINDA K. MCLOON · 2016 to 2026
$1.2M
VTA dopamine connectivity and functional responses to drugs of abuseR21DA056728 · NIDA · UNIVERSITY OF MINNESOTA · PI CHEN, ZHE, MEISEL, ROBERT L · 2023 to 2024
$426k
NEI NIH HHS R01 EY024261NEI NIH HHS R01 EY033316NEI NIH HHS T32 EY025187NIDA NIH HHS R21 DA056728
6 · The paper itself

Abstract

Norrin-induced activation of β-catenin-dependent signaling through the receptor frizzled4 in endothelial cells (ECs) is essential for establishing and maintaining blood-CNS barrier function. We sought to determine how this pathway is modulated under stress or disease conditions. Specifically, we investigated the role of p53 in endothelial blood-CNS barriers because increased abundance of the transcription factor p53 in ECs correlates with leaky CNS blood vessels in type 2 diabetes. Using transcriptomic, cell-based, and mouse genetic approaches, we identified interplay between p53 and its negative regulator MDM2 and norrin/frizzled4 signaling. Mice with an EC-specific ablation of

Indexed as

Blood-Brain BarrierEye ProteinsFrizzled ReceptorsNerve Tissue ProteinsProto-Oncogene Proteins c-mdm2Signal TransductionTumor Suppressor Protein p53AnimalsCell ProliferationEndothelial CellsHumansMiceMice, KnockoutEye ProteinsFrizzled ReceptorsFzd4 protein, mouseMdm2 protein, mouseNdph protein, mouseNerve Tissue ProteinsProto-Oncogene Proteins c-mdm2Trp53 protein, mouseTumor Suppressor Protein p53

Identifiers

PMID40627684
PMCPMC12288884

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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.