Evidence map›Paper›PMID 35552394›Full record

ArticleDevelopment (Cambridge, England)2022

The WNT7A/WNT7B/GPR124/RECK signaling module plays an essential role in mammalian limb development.

Yanshu Wang, Arjun Venkatesh, Jiajia Xu, Mingxin Xu, John Williams, Philip M Smallwood, Aaron James, Jeremy Nathans

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Development (Cambridge, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

12 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Case Report: Compound heterozygous variants inFrontiers in pediatrics · 2025
    Article
  9. The limb dorsoventral axis: Lmx1b's role in development, pathology, evolution, and regeneration.Developmental dynamics : an official publication of the American Association of Anatomists · 2024
    Review
  10. Article
  11. The development of hair follicles and nail.Developmental biology · 2024
    Review
  12. Article
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 at 2 institutions in 1 country.

Yanshu WangDepartment of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Arjun VenkateshDepartment of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Jiajia XuDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Mingxin XuDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
John WilliamsDepartment of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Philip M SmallwoodDepartment of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Aaron JamesDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.ORCID 0000-0002-2002-622X
Jeremy NathansDepartment of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.ORCID 0000-0001-8106-5460
Howard Hughes Medical Institute · USJohns Hopkins University · US

Funding

Howard Hughes Medical Institute
6 · The paper itself

Abstract

In central nervous system vascular endothelial cells, signaling via the partially redundant ligands WNT7A and WNT7B requires two co-activator proteins, GPR124 and RECK. WNT7A and RECK have been shown previously to play a role in limb development, but the mechanism of RECK action in this context is unknown. The roles of WNT7B and GPR124 in limb development have not been investigated. Using combinations of conventional and/or conditional loss-of-function alleles for mouse Wnt7a, Wnt7b, Gpr124 and Reck, including a Reck allele that codes for a protein that is specifically defective in WNT7A/WNT7B signaling, we show that reductions in ligand and/or co-activator function synergize to cause reduced and dysmorphic limb bone growth. Two additional limb phenotypes - loss of distal Lmx1b expression and ectopic growth of nail-like structures - occur with reduced Wnt7a/Wnt7b gene copy number and, respectively, with Reck mutations and with combined Reck and Gpr124 mutations. A third limb phenotype - bleeding into a digit - occurs with the most severe combinations of Wnt7a/Wnt7b, Reck and Gpr124 mutations. These data imply that the WNT7A/WNT7B-FRIZZLED-LRP5/LRP6-GPR124-RECK signaling system functions as an integral unit in limb development.

Indexed as

Receptors, G-Protein-CoupledWnt ProteinsAnimalsCentral Nervous SystemEmbryo, MammalianEndothelial CellsExtremitiesGPI-Linked ProteinsLigandsMiceProto-Oncogene ProteinsSignal TransductionGPI-Linked ProteinsGPR124 protein, mouseLigandsProto-Oncogene ProteinsReceptors, G-Protein-CoupledReck protein, mouseWnt7a protein, mouseWnt7b protein, mouseWnt ProteinsBlood-brain barrierLimb developmentMouseWnt signaling

Identifiers

PMID35552394
PMCPMC9148564
OpenAlexW4280550029

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.