ArticleGenetics2014
Genetic interactions between Shox2 and Hox genes during the regional growth and development of the mouse limb.
Article in Genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- A putativebioRxiv : the preprint server for biology · 2026Article
- Temporal constraints on enhancer usage shape the regulation of limb gene transcription.Nature communications · 2026Article
- Functional evidence supports the potential role of Tbx4-HLEA in the hindlimb degeneration of cetaceans.EvoDevo · 2025Article
- A gene desert required for regulatory control of pleiotropic Shox2 expression and embryonic survival.Nature communications · 2024Article
- Humero-femoral index and diabetes risk in the US population- a case study.Journal of diabetes and metabolic disorders · 2023Article
- Developmental Genetic Basis ofInternational journal of molecular sciences · 2023Article
- Interspecies transcriptomics identify genes that underlie disproportionate foot growth in jerboas.Current biology : CB · 2022Article
- Limb Mesoderm and Head Ectomesenchyme Both Express a Core Transcriptional Program During Chondrocyte Differentiation.Frontiers in cell and developmental biology · 2022Article
- All-trans-retinoic acid suppresses rat embryo hindlimb bud mesenchymal chondrogenesis by modulating HoxD9 expression.Bioengineered · 2021Article
- Zfhx4 regulates endochondral ossification as the transcriptional platform of Osterix in mice.Communications biology · 2021Article
- A Human Skeletal Muscle Atlas Identifies the Trajectories of Stem and Progenitor Cells across Development and from Human Pluripotent Stem Cells.Cell stem cell · 2020Article
- Bone morphology is regulated modularly by global and regional genetic programs.Development (Cambridge, England) · 2019Article
- Molecular signatures identify immature mesenchymal progenitors in early mouse limb buds that respond differentially to morphogen signaling.Development (Cambridge, England) · 2019Article
- Hoxa13 regulates expression of common Hox target genes involved in cartilage development to coordinate the expansion of the autopodal anlage.Development, growth & differentiation · 2019Article
- Hox genes in the adult skeleton: Novel functions beyond embryonic development.Developmental dynamics : an official publication of the American Association of Anatomists · 2017Review
- Accumulation of transposable elements in Hox gene clusters during adaptive radiation of Anolis lizards.Proceedings. Biological sciences · 2016Article
- A Track Record on SHOX: From Basic Research to Complex Models and Therapy.Endocrine reviews · 2016Review
- A unique stylopod patterning mechanism by Shox2-controlled osteogenesis.Development (Cambridge, England) · 2016Article
- A role for HOX13 proteins in the regulatory switch between TADs at the HoxD locus.Genes & development · 2016Article
- Regional Differential Genetic Response of Human Articular Cartilage to Impact Injury.Cartilage · 2016Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The growth and development of the vertebrate limb relies on homeobox genes of the Hox and Shox families, with their independent mutation often giving dose-dependent effects. Here we investigate whether Shox2 and Hox genes function together during mouse limb development by modulating their relative dosage and examining the limb for nonadditive effects on growth. Using double mRNA fluorescence in situ hybridization (FISH) in single embryos, we first show that Shox2 and Hox genes have associated spatial expression dynamics, with Shox2 expression restricted to the proximal limb along with Hoxd9 and Hoxa11 expression, juxtaposing the distal expression of Hoxa13 and Hoxd13. By generating mice with all possible dosage combinations of mutant Shox2 alleles and HoxA/D cluster deletions, we then show that their coordinated proximal limb expression is critical to generate normally proportioned limb segments. These epistatic interactions tune limb length, where Shox2 underexpression enhances, and Shox2 overexpression suppresses, Hox-mutant phenotypes. Disruption of either Shox2 or Hox genes leads to a similar reduction in Runx2 expression in the developing humerus, suggesting their concerted action drives cartilage maturation during normal development. While we furthermore provide evidence that Hox gene function influences Shox2 expression, this regulation is limited in extent and is unlikely on its own to be a major explanation for their genetic interaction. Given the similar effect of human SHOX mutations on regional limb growth, Shox and Hox genes may generally function as genetic interaction partners during the growth and development of the proximal vertebrate limb.
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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.