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All cases of FOP are caused by activating mutations in the type I BMP\/TGF\u03b2 cell surface receptor ACVR1, which over-activates signaling through phospho-Smad1\/5 (pSmad1\/5). To investigate the mechanism by which FOP-ACVR1 enhances pSmad1\/5 activation, we used zebrafish embryonic dorsoventral (DV) patterning as an assay for BMP signaling. We determined that the FOP mutants ACVR1-R206H and -G328R do not require their ligand binding domain to over-activate BMP signaling in DV patterning. However, intact ACVR1-R206H has the ability to respond to both Bmp7 and Activin A ligands. Additionally, BMPR1, a type I BMP receptor normally required for BMP-mediated patterning of the embryo, is dispensable for both ligand-independent signaling pathway activation and ligand-responsive signaling hyperactivation by ACVR1-R206H. These results demonstrate that FOP-ACVR1 is not constrained by the same receptor\/ligand partner requirements as WT-ACVR1.<\/jats:p>","DOI":"10.7554\/elife.53761","type":"journal-article","created":{"date-parts":[[2020,9,8]],"date-time":"2020-09-08T10:00:22Z","timestamp":1599559222000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.53761","source":"Crossref","is-referenced-by-count":36,"title":["Fibrodysplasia ossificans progressiva mutant ACVR1 signals by multiple modalities in the developing zebrafish"],"prefix":"10.7554","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8306-0620","authenticated-orcid":true,"given":"Robyn S","family":"Allen","sequence":"first","affiliation":[{"name":"Department of Cell and Developmental Biology University of Pennsylvania Perelman School of Medicine, Philadelphia, United States"},{"name":"Departments of Orthopaedic Surgery and Genetics University of Pennsylvania Perelman School of Medicine, Philadelphia, United 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