ArticleProceedings of the National Academy of Sciences of the United States of America2021
BMP heterodimers signal via distinct type I receptor class functions.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 59 citations in OpenAlex.
- Amhy/Amhr2y-mediated sex determination in two distantly related teleosts relies on the conserved Alk3-Smad5 axis.Molecular biology and evolution · 2026Article
- Chordin-mediated BMP shuttling patterns the secondary body axis in a cnidarian.Science advances · 2025Article
- Not all dimers are equal.eLife · 2025Article
- Mutations in the bone morphogenetic protein signaling pathway sensitize zebrafish and humans to ethanol-induced jaw malformations.Disease models & mechanisms · 2025Article
- Article
- Highly conserved and extremely evolvable: BMP signalling in secondary axis patterning of Cnidaria and Bilateria.Development genes and evolution · 2024Review
- Capitella teleta gets left out: possible evolutionary shift causes loss of left tissues rather than increased neural tissue from dominant-negative BMPR1.Neural development · 2024Article
- Analysis of SMAD1/5 target genes in a sea anemone reveals ZSWIM4-6 as a novel BMP signaling modulator.eLife · 2024Article
- Context-dependent TGFβ family signalling in cell fate regulation.Nature reviews. Molecular cell biology · 2023Review
- Reduced GS Domain Serine/Threonine Requirements of Fibrodysplasia Ossificans Progressiva Mutant Type I BMP Receptor ACVR1 in the Zebrafish.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Article
- Heterodimerization-dependent secretion of bone morphogenetic proteins in Drosophila.Developmental cell · 2023Article
- Progress of Wnt Signaling Pathway in Osteoporosis.Biomolecules · 2023Review
- Formation and characterization of BMP2/GDF5 and BMP4/GDF5 heterodimers.BMC biology · 2023Article
- Overexpression of Wild-Type ACVR1 in Fibrodysplasia Ossificans Progressiva Mice Rescues Perinatal Lethality and Inhibits Heterotopic Ossification.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- The context-dependent, combinatorial logic of BMP signaling.Cell systems · 2022Article
- Competition between type I activin and BMP receptors for binding to ACVR2A regulates signaling to distinct Smad pathways.BMC biology · 2022Article
- Coordination of iron homeostasis by bone morphogenetic proteins: Current understanding and unanswered questions.Developmental dynamics : an official publication of the American Association of Anatomists · 2022Article
- Functionally diverse heteromeric traps for ligands of the transforming growth factor-β superfamily.Scientific reports · 2021Article
- Heterodimer-heterotetramer formation mediates enhanced sensor activity in a biophysical model for BMP signaling.PLoS computational biology · 2021Article
- The BMP Pathway in Blood Vessel and Lymphatic Vessel Biology.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Heterodimeric TGF-β ligands outperform homodimers in a variety of developmental, cell culture, and therapeutic contexts; however, the mechanisms underlying this increased potency remain uncharacterized. Here, we use dorsal-ventral axial patterning of the zebrafish embryo to interrogate the BMP2/7 heterodimer signaling mechanism. We demonstrate that differential interactions with BMP antagonists do not account for the reduced signaling ability of homodimers. Instead, we find that while overexpressed BMP2 homodimers can signal, they require two nonredundant type I receptors, one from the Acvr1 subfamily and one from the Bmpr1 subfamily. This implies that all BMP signaling within the zebrafish gastrula, even BMP2 homodimer signaling, requires Acvr1. This is particularly surprising as BMP2 homodimers do not bind Acvr1 in vitro. Furthermore, we find that the roles of the two type I receptors are subfunctionalized within the heterodimer signaling complex, with the kinase activity of Acvr1 being essential, while that of Bmpr1 is not. These results suggest that the potency of the Bmp2/7 heterodimer arises from the ability to recruit both Acvr1 and Bmpr1 into the same signaling complex.
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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.