GPR124 regulates hyaloid blood vessel regression and is associated with endothelial-mesenchymal transition.

Overview

Authors: Laura Hannig^1,2, Robin Heiden¹, Süleyman Ergün^1,3, Barbara M Braunger^1,2, Mario Vallon¹

Institute of Anatomy and Cell Biology, University of Würzburg, Würzburg, Germany
Present Address: Institute of Neuroanatomy, University Hospital Hamburg-Eppendorf, Hamburg, Germany
Atlas University Research Center (ARC), Istanbul Atlas University, Istanbul, Turkey

Institutions: University of Würzburg (Germany); University Medical Center Hamburg-Eppendorf (Germany); Atlas Üniversitesi

Journal: Scientific reports, volume 16, issue 1, article 13765

Dates: received 5 July 2025; accepted 23 April 2026; published online 29 April 2026

Type: Research article · Language: English

License: CC BY

Identifiers: DOI 10.1038/s41598-026-50835-1 · PMID 42056280 · PMCID PMC13128929 · OpenAlex W7158577171

Open access: gold, a free copy (OpenAlex)

Status: data only

Categories: mouse (organism), cellular / molecular (subfield)

Methods: Statistics, Smoothing, state filtering, decompositions, Machine learning

Keywords: Cell biology, Molecular biology

MeSH: Endothelial-Mesenchymal Transition*, Receptors, G-Protein-Coupled*, Retinal Vessels*, Animals, Apoptosis, Endothelial Cells, Mice, Mice, Knockout, Wnt Signaling Pathway (* major topic)

Topic: Developmental Biology and Gene Regulation (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex

Funding: Julius-Maximilians-Universität Würzburg

Citations: not cited yet (Europe PMC); 38 references in the paper

Abstract

Transition from the transient hyaloid vasculature to the mature retinal vascular network is a critical step in mammalian eye development. While WNT7B signaling in endothelial cells regulates programmed hyaloid vessel regression, the specific receptors and downstream mechanisms remain poorly defined. Here, we identify GPR124, a ligand-specific co-receptor for WNT7A/B, as a key regulator of this process. Using an endothelial-specific, tamoxifen-inducible Gpr124 knockout mouse model, we show that loss of GPR124 in hyaloid endothelium markedly impairs postnatal hyaloid vessel clearance. Notably, GPR124 function in the developing eye was highly compartment-specific: although crucial for hyaloid vessel regression, it was dispensable for retinal angiogenesis, despite being expressed in both vascular beds. Gpr124 deletion led to downregulation of several established WNT target genes in hyaloid endothelial cells, consistent with a role for GPR124 in mediating WNT/β-catenin signaling, as previously shown in brain endothelium. While GPR124 was not required for induction of isolated apoptotic events in hyaloid vessels, it promoted segmental vessel regression, characterized by linear clusters of apoptotic endothelial cells. Single-cell RNA sequencing of hyaloid endothelial cells, combined with immunostaining, revealed transcriptional changes consistent with partial endothelial-mesenchymal transition (EndMT). Our findings identify GPR124 as a key mediator of hyaloid vessel regression and suggest that GPR124-dependent WNT/β-catenin signaling and EndMT may contribute to vascular remodeling during ocular development.

Supplementary Information: The online version contains supplementary material available at 10.1038/s41598-026-50835-1.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Datasets cited

geo:GSE199858, at NCBI GEO; found in the text, “GPR124 does not modulate retinal angiogenesis”

Data availability

Raw and processed single-cell RNA sequencing data have been deposited in Gene Expression Omnibus (GEO) under accession number [GSE284257 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE284257)] (https:/www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE284257).

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 5 authors, 2 keywords, 9 MeSH terms, 1 funder, 38 references.

Cite

This paper

Hannig, L., Heiden, R., Ergün, S., Braunger, B. M., & Vallon, M. (2026). GPR124 regulates hyaloid blood vessel regression and is associated with endothelial-mesenchymal transition. Scientific reports, 16(1), 13765. https://doi.org/10.1038/s41598-026-50835-1

BibTeX

@article{hannig2026gpr124, author = {Hannig, Laura and Heiden, Robin and Ergün, Süleyman and Braunger, Barbara M and Vallon, Mario}, title = {{GPR124 regulates hyaloid blood vessel regression and is associated with endothelial-mesenchymal transition}}, journal = {Scientific reports}, year = {2026}, month = apr, volume = {16}, number = {1}, pages = {13765}, publisher = {Nature Publishing Group}, issn = {2045-2322}, doi = {10.1038/s41598-026-50835-1}, url = {https://doi.org/10.1038/s41598-026-50835-1}, pmid = {42056280}, pmcid = {PMC13128929} }

RIS

TY - JOUR AU - Hannig, Laura AU - Heiden, Robin AU - Ergün, Süleyman AU - Braunger, Barbara M AU - Vallon, Mario TI - GPR124 regulates hyaloid blood vessel regression and is associated with endothelial-mesenchymal transition T2 - Scientific reports J2 - Sci Rep PY - 2026 DA - 2026/04/29 VL - 16 IS - 1 SP - 13765 SN - 2045-2322 PB - Nature Publishing Group DO - 10.1038/s41598-026-50835-1 UR - https://doi.org/10.1038/s41598-026-50835-1 LA - en ER -

CSL-JSON

{ "id": "10.1038/s41598-026-50835-1", "type": "article-journal", "title": "GPR124 regulates hyaloid blood vessel regression and is associated with endothelial-mesenchymal transition", "container-title": "Scientific reports", "author": [ { "family": "Hannig", "given": "Laura" }, { "family": "Heiden", "given": "Robin" }, { "family": "Ergün", "given": "Süleyman" }, { "family": "Braunger", "given": "Barbara M" }, { "family": "Vallon", "given": "Mario" } ], "container-title-short": "Sci Rep", "volume": "16", "issue": "1", "page": "13765", "DOI": "10.1038/s41598-026-50835-1", "PMID": "42056280", "PMCID": "PMC13128929", "ISSN": "2045-2322", "publisher": "Nature Publishing Group", "URL": "https://doi.org/10.1038/s41598-026-50835-1", "language": "en", "issued": { "date-parts": [ [ 2026, 4, 29 ] ] } }

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Sign in with ORCID to claim this paper as one of its authors, correct its record or validate its tracing map: when the paper's metadata lists your ORCID iD, you are recognized at once. Maintainers of its code: sign in with GitHub, then claim the repository on your account page.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion, reproductions, activity

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.