ArticleDevelopment (Cambridge, England)2014
Nkx2-5 regulates cardiac growth through modulation of Wnt signaling by R-spondin3.
Article in Development (Cambridge, England), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Pooled it
- Review
- Article
- Regulation of RSPO3-LGR4 Signaling: Emerging Role in Inflammation Revealed by Network Analysis.Archives of clinical and biomedical research · 2025Article
- In Vitro Models of Cardiovascular Disease: Embryoid Bodies, Organoids and Everything in Between.Biomedicines · 2024Review
- The G4 resolvase Dhx36 modulates cardiomyocyte differentiation and ventricular conduction system development.Nature communications · 2024Article
- Standardized production of hPSC-derived cardiomyocyte aggregates in stirred spinner flasks.Nature protocols · 2024Article
- RSPO3 induced by Helicobacter pylori extracts promotes gastric cancer stem cell properties through the GNG7/β-catenin signaling pathway.Cancer medicine · 2024Article
- Deletion of Sarcolemmal Membrane-Associated Protein Isoform 3 (SLMAP3) in Cardiac Progenitors Delays Embryonic Growth of Myocardium without Affecting Hippo Pathway.International journal of molecular sciences · 2024Article
- Streamlined identification of clinically and functionally relevant genetic regulators of lower-tract urogenital development.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The overexpression of R-spondin 3 affects hair morphogenesis and hair development along with the formation and maturation of the hair follicle stem cells.Frontiers in physiology · 2024Article
- An Anterior Second Heart Field Enhancer Regulates the Gene Regulatory Network of the Cardiac Outflow Tract.Circulation · 2023Article
- Endothelial cell-derived RSPO3 activates Gαi1/3-Erk signaling and protects neurons from ischemia/reperfusion injury.Cell death & disease · 2023Article
- Knockout of the Cardiac Transcription Factor NKX2-5 Results in Stem Cell-Derived Cardiac Cells with Typical Purkinje Cell-like Signal Transduction and Extracellular Matrix Formation.International journal of molecular sciences · 2023Article
- Overlapping functions of SIX homeoproteins during embryonic myogenesis.PLoS genetics · 2023Article
- Nkx2.5: a crucial regulator of cardiac development, regeneration and diseases.Frontiers in cardiovascular medicine · 2023Review
- Transcriptomic Changes Associated withCancers · 2022Article
- Single-cell atlas of multilineage cardiac organoids derived from human induced pluripotent stem cells.Life medicine · 2022Article
- The role of roof plate-specific spondins in liver homeostasis and disease.Liver research (Beijing, China) · 2022Review
- In silico functional and pathway analysis of risk genes and SNPs for type 2 diabetes in Asian population.PloS one · 2022Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
A complex regulatory network of morphogens and transcription factors is essential for normal cardiac development. Nkx2-5 is among the earliest known markers of cardiac mesoderm that is central to the regulatory pathways mediating second heart field (SHF) development. Here, we have examined the specific requirements for Nkx2-5 in the SHF progenitors. We show that Nkx2-5 potentiates Wnt signaling by regulating the expression of the R-spondin3 (Rspo3) gene during cardiogenesis. R-spondins are secreted factors and potent Wnt agonists that in part regulate stem cell proliferation. Our data show that Rspo3 is markedly downregulated in Nkx2-5 mutants and that Rspo3 expression is regulated by Nkx2-5. Conditional inactivation of Rspo3 in the Isl1 lineage resulted in embryonic lethality secondary to impaired development of SHF. More importantly, we find that Wnt signaling is significantly attenuated in Nkx2-5 mutants and that enhancing Wnt/β-catenin signaling by pharmacological treatment or by transgenic expression of Rspo3 rescues the SHF defects in the conditional Nkx2-5(+/-) mutants. We have identified a previously unrecognized genetic link between Nkx2-5 and Wnt signaling that supports continued cardiac growth and proliferation during development. Identification of Rspo3 in cardiac development provides a new paradigm in temporal regulation of Wnt signaling by cardiac-specific transcription factors.
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Registered trials
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.