ArticlePLoS genetics2012
Multiple roles and interactions of Tbx4 and Tbx5 in development of the respiratory system.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers, 1 of them a synthesis that pooled it.
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Who cites it
133 citing papers in PubMed, 1 synthesis or guideline pooled it, 211 citations in OpenAlex.
- DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis.American journal of human genetics · 2016Pooled it
- Variant Class-Specific Phenotypes and Outcomes in Pediatric TBX4-Associated Pulmonary Hypertension.Pediatric pulmonology · 2026Article
- Article
- Comparative Transcriptomics of Feather Follicles Reveals Potential Candidate Genes for Duck Feather Type Differentiation.Animals : an open access journal from MDPI · 2026Article
- Pulmonary arterial hypertension from a translational perspective: Bridging pathophysiology and treatment.Chinese medical journal · 2026Review
- Adverse and adaptive placental DNA methylation changes linking prenatal air pollution exposure to child lung function: findings from the SEPAGES cohort.EBioMedicine · 2026Article
- Excessive postnatal smooth muscle differentiation in a lung-specific model of TBX4-related pulmonary hypertension.JCI insight · 2026Article
- Sotatercept in TBX4 Associated Heritable Pulmonary Arterial Hypertension: A Case Report of a Super Responder.Pulmonary circulation · 2026Article
- Article
- Inherited TBX4 frameshifting variants predicted to escape nonsense mediated decay in two families with variable phenotypes, including lethal lung developmental disorders.Human genomics · 2026Article
- Chromosome 17q23.1-q23.2 deletion syndrome with severe pulmonary hypertension in neonates: two case reports and literature review.BMC pediatrics · 2026Review
- Multifaceted role of T-box transcription factor 4: From embryonic development to disease pathogenesis.Genes & diseases · 2026Review
- Postnatally induced TBX4 insufficiency confers pulmonary hypertension and impairs lung development in infant mice.Pediatric research · 2026Article
- Complex Genomic Rearrangement Involving theHuman mutation · 2026Article
- Face-mask CPAP as palliative support for diffuse tracheobronchomalacia from ring agenesis in an infant: When sleep becomes therapeutic.Respiratory medicine case reports · 2026Article
- HOXA5-driven transcriptional program in lung development.Developmental biology · 2025Article
- Stromagenesis and cancer-associated fibroblast heterogeneity in primary tumors and metastasis: focus in non-small cell lung cancer.FEBS open bio · 2025Review
- TBX4 in Pulmonary Hypertension: Linking Lung Development to Precision Therapy.American journal of respiratory cell and molecular biology · 2025Article
- Loss ofAmerican journal of respiratory cell and molecular biology · 2025Article
- Emerging Concepts in Fibroblast Biology and Progressive Pulmonary Fibrosis.Seminars in respiratory and critical care medicine · 2025Review
73 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Normal development of the respiratory system is essential for survival and is regulated by multiple genes and signaling pathways. Both Tbx4 and Tbx5 are expressed throughout the mesenchyme of the developing lung and trachea; and, although multiple genes are known to be required in the epithelium, only Fgfs have been well studied in the mesenchyme. In this study, we investigated the roles of Tbx4 and Tbx5 in lung and trachea development using conditional mutant alleles and two different Cre recombinase transgenic lines. Loss of Tbx5 leads to a unilateral loss of lung bud specification and absence of tracheal specification in organ culture. Mutants deficient in Tbx4 and Tbx5 show severely reduced lung branching at mid-gestation. Concordant with this defect, the expression of mesenchymal markers Wnt2 and Fgf10, as well as Fgf10 target genes Bmp4 and Spry2, in the epithelium is downregulated. Lung branching undergoes arrest ex vivo when Tbx4 and Tbx5 are both completely lacking. Lung-specific Tbx4 heterozygous;Tbx5 conditional null mice die soon after birth due to respiratory distress. These pups have small lungs and show severe disruptions in tracheal/bronchial cartilage rings. Sox9, a master regulator of cartilage formation, is expressed in the trachea; but mesenchymal cells fail to condense and consequently do not develop cartilage normally at birth. Tbx4;Tbx5 double heterozygous mutants show decreased lung branching and fewer tracheal cartilage rings, suggesting a genetic interaction. Finally, we show that Tbx4 and Tbx5 interact with Fgf10 during the process of lung growth and branching but not during tracheal/bronchial cartilage development.
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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.