ArticlePLoS biology2021
The BMP signaling gradient is interpreted through concentration thresholds in dorsal-ventral axial patterning.
Article in PLoS biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 50 citations in OpenAlex.
- Sharp cell type boundaries emerge from coordinated morphogen signaling.Genes & development · 2026Article
- Biochemical principles of SMAD signaling across the animal kingdom.The Biochemical journal · 2026Review
- An optogenetic toolkit for robust activation of FGF, BMP, & Nodal signaling in zebrafish.Developmental biology · 2026Article
- Interpretable decoding of cell fate from a snapshot of combinatorial signaling.bioRxiv : the preprint server for biology · 2026Article
- EpicTope: predicting and validating non-disruptive epitope tagging sites.Development (Cambridge, England) · 2026Article
- Temporal regulation of endoderm convergence and extension by the BMP activity gradient through mesoderm-dependent and independent mechanisms.Cells & development · 2025Article
- Mutual repression between Pax2 and Snail factors regulates the epithelial/mesenchymal state during intermediate mesoderm differentiation.Development (Cambridge, England) · 2025Article
- Chordin-mediated BMP shuttling patterns the secondary body axis in a cnidarian.Science advances · 2025Article
- Temporal dynamics of BMP/Nodal ratio drive tissue-specific gastrulation morphogenesis.Development (Cambridge, England) · 2025Article
- The Role of Adenogenesis Factors in the Pathogenesis of Endometriosis.International journal of molecular sciences · 2025Review
- Discoidin domain receptor 2 is an important modulator of BMP signaling during heterotopic bone formation.Bone research · 2025Article
- Short-range Fgf signalling patterns hindbrain progenitors to induce the neurogenesis-to-oligodendrogenesis switch.Development (Cambridge, England) · 2024Article
- Target gene responses differ when transcription factor levels are acutely decreased by nuclear export versus degradation.Development (Cambridge, England) · 2024Article
- Sizzled (Frzb3) physically interacts with noncanonical Wnt ligands to inhibit gastrulation cell movement.Molecules and cells · 2024Article
- Highly conserved and extremely evolvable: BMP signalling in secondary axis patterning of Cnidaria and Bilateria.Development genes and evolution · 2024Review
- HBO1 determines SMAD action in pluripotency and mesendoderm specification.Nucleic acids research · 2024Article
- Target gene responses differ when transcription factor levels are acutely decreased by nuclear export versus degradation.bioRxiv : the preprint server for biology · 2024Article
- Time-integrated BMP signaling determines fate in a stem cell model for early human development.Nature communications · 2024Article
- Robust axis elongation by Nodal-dependent restriction of BMP signaling.Development (Cambridge, England) · 2024Article
- Analysis of SMAD1/5 target genes in a sea anemone reveals ZSWIM4-6 as a novel BMP signaling modulator.eLife · 2024Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Bone Morphogenetic Protein (BMP) patterns the dorsal-ventral (DV) embryonic axis in all vertebrates, but it is unknown how cells along the DV axis interpret and translate the gradient of BMP signaling into differential gene activation that will give rise to distinct cell fates. To determine the mechanism of BMP morphogen interpretation in the zebrafish gastrula, we identified 57 genes that are directly activated by BMP signaling. By using Seurat analysis of single-cell RNA sequencing (scRNA-seq) data, we found that these genes are expressed in at least 3 distinct DV domains of the embryo. We distinguished between 3 models of BMP signal interpretation in which cells activate distinct gene expression through interpretation of thresholds of (1) the BMP signaling gradient slope; (2) the BMP signal duration; or (3) the level of BMP signal activation. We tested these 3 models using quantitative measurements of phosphorylated Smad5 (pSmad5) and by examining the spatial relationship between BMP signaling and activation of different target genes at single-cell resolution across the embryo. We found that BMP signaling gradient slope or BMP exposure duration did not account for the differential target gene expression domains. Instead, we show that cells respond to 3 distinct levels of BMP signaling activity to activate and position target gene expression. Together, we demonstrate that distinct pSmad5 threshold levels activate spatially distinct target genes to pattern the DV axis.
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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.