ArticleDevelopmental dynamics : an official publication of the American Association of Anatomists2014
Tbx4 interacts with the short stature homeobox gene Shox2 in limb development.
Article in Developmental dynamics : an official publication of the American Association of Anatomists, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Multifaceted role of T-box transcription factor 4: From embryonic development to disease pathogenesis.Genes & diseases · 2026Review
- Temporal constraints on enhancer usage shape the regulation of limb gene transcription.Nature communications · 2026Article
- Linking shox/shox2 deficiency with fgfr3 gain-of-function and natriuretic peptides.Frontiers in endocrinology · 2026Article
- Convergent evolution of noncoding elements associated with short tarsus length in birds.BMC biology · 2025Article
- Identification and Functional Evaluation of a NovelInternational journal of molecular sciences · 2022Article
- Tbx4 function during hindlimb development reveals a mechanism that explains the origins of proximal limb defects.Development (Cambridge, England) · 2021Article
- Rare andJournal of medical genetics · 2020Article
- Detection of SHOX2 DNA methylation by methylation-specific PCR in non-small cell lung cancer.Translational cancer research · 2020Article
- The role of genomics and genetics in pulmonary arterial hypertension.Global cardiology science & practice · 2020Review
- Molecular genetic framework underlying pulmonary arterial hypertension.Nature reviews. Cardiology · 2020Review
- Homozygous Null TBX4 Mutations Lead to Posterior Amelia with Pelvic and Pulmonary Hypoplasia.American journal of human genetics · 2019Article
- T-box family of transcription factor-TBX5, insights in development and disease.American journal of translational research · 2017Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundThe short stature homeodomain transcription factors SHOX and SHOX2 play key roles in limb formation. To gain more insight into genes regulated by Shox2 during limb development, we analyzed expression profiles of WT and Shox2-/- mouse embryonic limbs and identified the T-Box transcription factor Tbx4 as a potential downstream target. Tbx4 is known to exert essential functions in skeletal and muscular hindlimb development. In humans, haploinsufficiency of TBX4 causes small patella syndrome, a skeletal dysplasia characterized by anomalies of the knee, pelvis, and foot.
resultsHere, we demonstrate an inhibitory regulatory effect of Shox2 on Tbx4 specifically in the forelimbs. We also show that Tbx4 activates Shox2 expression in fore- and hindlimbs, suggesting Shox2 as a feedback modulator of Tbx4. Using EMSA studies, we find that Tbx4/TBX4 is able to bind to distinct T-box binding sites within the mouse and human Shox2/SHOX2 promoter.
conclusionsOur data identifies Tbx4 as a novel transcriptional activator of Shox2 during murine fore- and hindlimb development. Tbx4 is also regulated by Shox2 specifically in the forelimb bud possibly via a feedback mechanism. These data extend our understanding of the role and regulation of Tbx4 and Shox2 in limb development and limb associated diseases.
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