ArticleJCI insight2017
Wnt11 regulates cardiac chamber development and disease during perinatal maturation.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- In Vivo Models of Cardiovascular Disease:Biomedicines · 2025Review
- The molecular mechanisms of cardiac development and related diseases.Signal transduction and targeted therapy · 2024Review
- SMC3 contributes to heart development by regulating super-enhancer associated genes.Experimental & molecular medicine · 2024Article
- Telocytes: current methods of research, challenges and future perspectives.Cell and tissue research · 2024Review
- Post-Transcriptional Modification by Alternative Splicing and Pathogenic Splicing Variants in Cardiovascular Development and Congenital Heart Defects.International journal of molecular sciences · 2023Review
- Dynamic Involvement of Telocytes in Modulating Multiple Signaling Pathways in Cardiac Cytoarchitecture.International journal of molecular sciences · 2022Review
- WNT11, a new gene associated with early onset osteoporosis, is required for osteoblastogenesis.Human molecular genetics · 2022Article
- Article
- Roles of Wnt Signaling Pathway and ROR2 Receptor in Embryonic Development: An Update Review Article.Epigenetics insights · 2022Article
- Functional coordination of non-myocytes plays a key role in adult zebrafish heart regeneration.EMBO reports · 2021Article
- Recessive ciliopathy mutations in primary endocardial fibroelastosis: a rare neonatal cardiomyopathy in a case of Alstrom syndrome.Journal of molecular medicine (Berlin, Germany) · 2021Article
- Cardiac Wnt5a and Wnt11 promote fibrosis by the crosstalk of FZD5 and EGFR signaling under pressure overload.Cell death & disease · 2021Article
- Investigation of candidate genes and mechanisms underlying obesity associated type 2 diabetes mellitus using bioinformatics analysis and screening of small drug molecules.BMC endocrine disorders · 2021Article
- Oxygen injury in neonates: which is worse? hyperoxia, hypoxia, or alternating hyperoxia/hypoxia.Journal of lung, pulmonary & respiratory research · 2020Article
- Gene-environment regulatory circuits of right ventricular pathology in tetralogy of fallot.Journal of molecular medicine (Berlin, Germany) · 2019Article
- Stem Cell Therapy for Hypoplastic Left Heart Syndrome: Mechanism, Clinical Application, and Future Directions.Circulation research · 2018Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Ventricular chamber growth and development during perinatal circulatory transition is critical for functional adaptation of the heart. However, the chamber-specific programs of neonatal heart growth are poorly understood. We used integrated systems genomic and functional biology analyses of the perinatal chamber specific transcriptome and we identified Wnt11 as a prominent regulator of chamber-specific proliferation. Importantly, downregulation of Wnt11 expression was associated with cyanotic congenital heart defect (CHD) phenotypes and correlated with O2 saturation levels in hypoxemic infants with Tetralogy of Fallot (TOF). Perinatal hypoxia treatment in mice suppressed Wnt11 expression and induced myocyte proliferation more robustly in the right ventricle, modulating Rb1 protein activity. Wnt11 inactivation was sufficient to induce myocyte proliferation in perinatal mouse hearts and reduced Rb1 protein and phosphorylation in neonatal cardiomyocytes. Finally, downregulated Wnt11 in hypoxemic TOF infantile hearts was associated with Rb1 suppression and induction of proliferation markers. This study revealed a previously uncharacterized function of Wnt11-mediated signaling as an important player in programming the chamber-specific growth of the neonatal heart. This function influences the chamber-specific development and pathogenesis in response to hypoxia and cyanotic CHDs. Defining the underlying regulatory mechanism may yield chamber-specific therapies for infants born with CHDs.
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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.