ArticleDevelopment (Cambridge, England)2021
SMAD4 target genes are part of a transcriptional network that integrates the response to BMP and SHH signaling during early limb bud patterning.
Article in Development (Cambridge, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 16 citations in OpenAlex.
- Stimulation of Adult Muscle Stem Cells with BMPs Results in Direct Activation of Notch Pathway Genes.Cells · 2026Article
- Ultrasound-responsive hydrogels for bone and cartilage tissue engineering.Materials today. Bio · 2025Review
- Restoration of myogenesis in ALS-myocytes through miR-26a-5p-mediated Smad4 inhibition and its impact on motor neuron development.Molecular therapy. Nucleic acids · 2025Article
- Article
- The sonic hedgehog signaling inhibitor cyclopamine improves pulmonary arterial hypertension via regulating the bone morphogenetic protein receptor 2 pathway.Scientific reports · 2025Article
- Single-cell profiling of penta- and tetradactyl mouse limb buds identifies mesenchymal progenitors controlling digit numbers and identities.Nature communications · 2025Article
- TBX3 is essential for establishment of the posterior boundary of anterior genes and upregulation of posterior genes together with HAND2 during the onset of limb bud development.Development (Cambridge, England) · 2024Article
- Recombinant Limb Assay asFrontiers in cell and developmental biology · 2022Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
SMAD4 regulates gene expression in response to BMP and TGFβ signal transduction, and is required for diverse morphogenetic processes, but its target genes have remained largely elusive. Here, we identify the SMAD4 target genes in mouse limb buds using an epitope-tagged Smad4 allele for ChIP-seq analysis in combination with transcription profiling. This analysis shows that SMAD4 predominantly mediates BMP signal transduction during early limb bud development. Unexpectedly, the expression of cholesterol biosynthesis enzymes is precociously downregulated and intracellular cholesterol levels are reduced in Smad4-deficient limb bud mesenchymal progenitors. Most importantly, our analysis reveals a predominant function of SMAD4 in upregulating target genes in the anterior limb bud mesenchyme. Analysis of differentially expressed genes shared between Smad4- and Shh-deficient limb buds corroborates this function of SMAD4 and also reveals the repressive effect of SMAD4 on posterior genes that are upregulated in response to SHH signaling. This analysis uncovers opposing trans-regulatory inputs from SHH- and SMAD4-mediated BMP signal transduction on anterior and posterior gene expression during the digit patterning and outgrowth in early limb buds.
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