ArticleGenes & development2004
Mouse limb deformity mutations disrupt a global control region within the large regulatory landscape required for Gremlin expression.
Article in Genes & development, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 142 citations in OpenAlex.
- Pooled it
- Ancient genomic linkage of α-globin and Nprl3 couples metabolism with erythropoiesis.Nature communications · 2025Article
- Single-cell profiling of penta- and tetradactyl mouse limb buds identifies mesenchymal progenitors controlling digit numbers and identities.Nature communications · 2025Article
- The enhancer module of Integrator controls cell identity and early neural fate commitment.Nature cell biology · 2025Article
- Tgfbr1 controls developmental plasticity between the hindlimb and external genitalia by remodeling their regulatory landscape.Nature communications · 2024Article
- Probing the ligand binding specificity of FNBP4 WW domains and interaction with FH1 domain of FMN1.Current research in structural biology · 2024Article
- Association betweenGenes · 2023Article
- Ancient genomic linkage couples metabolism with erythroid development.bioRxiv : the preprint server for biology · 2023Article
- Genetic cold cases: lessons from solving complex congenital limb disorders.Genes & development · 2023Review
- Review
- Spatial regulation by multiple Gremlin1 enhancers provides digit development with cis-regulatory robustness and evolutionary plasticity.Nature communications · 2021Article
- Gremlin 1 - small protein, big impact: the multiorgan consequences of disrupted BMP antagonismThe Journal of pathology · 2020Article
- Stage-specific regulation of Gremlin1 on the differentiation and expansion of human urinary induced pluripotent stem cells into endothelial progenitors.Journal of cellular and molecular medicine · 2020Article
- WNT Signaling and Bone: Lessons From Skeletal Dysplasias and Disorders.Frontiers in endocrinology · 2020Review
- Molecular signatures identify immature mesenchymal progenitors in early mouse limb buds that respond differentially to morphogen signaling.Development (Cambridge, England) · 2019Article
- A Review of the Genetics and Pathogenesis of Syndactyly in Humans and Experimental Animals: A 3-Step Pathway of Pathogenesis.BioMed research international · 2019Review
- Promoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions.Journal of visualized experiments : JoVE · 2018Article
- Deletion of a Long-RangeGenetics · 2018Article
- Deleting the mouse Hsd17b1 gene results in a hypomorphic Naglu allele and a phenotype mimicking a lysosomal storage disease.Scientific reports · 2017Article
- John Saunders' ZPA, Sonic hedgehog and digit identity - How does it really all work?Developmental biology · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mouse limb deformity (ld) mutations cause limb malformations by disrupting epithelial-mesenchymal signaling between the polarizing region and the apical ectodermal ridge. Formin was proposed as the relevant gene because three of the five ld alleles disrupt its C-terminal domain. In contrast, our studies establish that the two other ld alleles directly disrupt the neighboring Gremlin gene, corroborating the requirement of this BMP antagonist for limb morphogenesis. Further doubts concerning an involvement of Formin in the ld limb phenotype are cast, as a targeted mutation removing the C-terminal Formin domain by frame shift does not affect embryogenesis. In contrast, the deletion of the corresponding genomic region reproduces the ld limb phenotype and is allelic to mutations in Gremlin. We resolve these conflicting results by identifying a cis-regulatory region within the deletion that is required for Gremlin activation in the limb bud mesenchyme. This distant cis-regulatory region within Formin is also altered by three of the ld mutations. Therefore, the ld limb bud patterning defects are not caused by disruption of Formin, but by alteration of a global control region (GCR) required for Gremlin transcription. Our studies reveal the large genomic landscape harboring this GCR, which is required for tissue-specific coexpression of two structurally and functionally unrelated genes.
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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.