{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T01:01:14Z","timestamp":1777424474277,"version":"3.51.4"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,3,25]],"date-time":"2019-03-25T00:00:00Z","timestamp":1553472000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["anatomypubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>This study analyzes <jats:italic>Prx1<\/jats:italic>\u2010specific conditional knockout of <jats:italic>Acvr1<\/jats:italic> aiming to elucidate the endogenous role of <jats:italic>Acvr1<\/jats:italic> during limb formation in early embryonic development. ACVR1 can exhibit activating and inhibiting function in BMP signaling. <jats:italic>ACVR1<\/jats:italic> gain\u2010of\u2010function mutations can cause the rare disease fibrodysplasia ossificans progressiva (FOP), where patients develop ectopic bone replacing soft tissue, tendons and ligaments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole\u2010mount in situ hybridization and skeletal preparations revealed that following limb\u2010specific conditional knockout of <jats:italic>Acvr1<\/jats:italic>, metacarpals and proximal phalanges were shortened and additional cartilage and bone elements were formed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The analysis of a set of marker genes including ligands and receptors of BMP signaling as well as genes involved in patterning and tendon and cartilage formation, revealed temporal disturbances with distinct spatial patterns. The most striking result was that in the absence of <jats:italic>Acvr1<\/jats:italic> in mesoderm precursor cells, first digits were drastically malformed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In FOP, malformation of big toes can serve as a first soft marker in diagnostics. The surprising similarities in phenotype between the described conditional knockout of <jats:italic>Acvr1<\/jats:italic> and the FOP mouse model, indicates a natural inhibitory function of ACVR1. This represents a further step towards better understanding the role of Acvr1 and developing treatment options for FOP.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dvdy.24","type":"journal-article","created":{"date-parts":[[2019,3,11]],"date-time":"2019-03-11T00:59:27Z","timestamp":1552265967000},"page":"396-403","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Limb specific Acvr1\u2010knockout during embryogenesis in mice exhibits great toe malformation as seen in Fibrodysplasia Ossificans Progressiva (FOP)"],"prefix":"10.1002","volume":"248","author":[{"given":"Laura","family":"Hildebrand","sequence":"first","affiliation":[{"name":"Berlin\u2010Brandenburg Center for Regenerative Therapies (BCRT) \/ Charit\u00e9 Virchow Campus  Berlin Germany"},{"name":"Charit\u00e9\u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Berlin Brandenburg School for Regenerative Therapies (BSRT)  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mareen","family":"Schmidt\u2010von Kegler","sequence":"additional","affiliation":[{"name":"Berlin\u2010Brandenburg Center for Regenerative Therapies (BCRT) \/ Charit\u00e9 Virchow Campus  Berlin Germany"},{"name":"Charit\u00e9\u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Walther","sequence":"additional","affiliation":[{"name":"Berlin\u2010Brandenburg Center for Regenerative Therapies (BCRT) \/ Charit\u00e9 Virchow Campus  Berlin Germany"},{"name":"Charit\u00e9\u2013 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6056-6669","authenticated-orcid":false,"given":"Petra","family":"Seemann","sequence":"additional","affiliation":[{"name":"Berlin\u2010Brandenburg Center for Regenerative Therapies (BCRT) \/ Charit\u00e9 Virchow Campus  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Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,3,25]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2009.02.012"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.150.3698.893"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvp148"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.35.21345"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2007.06187.x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7007-7-59"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2016.10.001"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-015-0104-z"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2008.05.013"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.010280"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2011.09.060"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02513"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.22779"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1999.9378"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2681"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1993.1184"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/gene.10092"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2012.12.008"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/wdev.59"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(06)00049-2"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1637"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.22565"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aac4358"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1510540112"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2008-0576"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaf1090"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3304"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2515"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.128.19.3855"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5368.1455"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI3459"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2005.07.016"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5275.613"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.128.22.4523"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1530\/JME-14-0062"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2385"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/gene.10015"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21021"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(01)00639-6"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2002.0640"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00530"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.3.605"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mod.2004.11.005"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25118"},{"key":"e_1_2_6_46_1","unstructured":"StangeK.Skelettfehlbildungen 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