{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:44:46Z","timestamp":1791845086718,"version":"4.3.4"},"reference-count":38,"publisher":"The Company of Biologists","issue":"3","license":[{"start":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T00:00:00Z","timestamp":1679616000000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"crossref","award":["5R37AR047709"],"award-info":[{"award-number":["5R37AR047709"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Human Robinow syndrome (RS) and dominant omodysplasia type 2 (OMOD2), characterized by skeletal limb and craniofacial defects, are associated with heterozygous mutations in the Wnt receptor FZD2. However, as FZD2 can activate both canonical and non-canonical Wnt pathways, its precise functions and mechanisms of action in limb development are unclear. To address these questions, we generated mice harboring a single-nucleotide insertion in Fzd2 (Fzd2em1Smill), causing a frameshift mutation in the final Dishevelled-interacting domain. Fzd2em1Smill mutant mice had shortened limbs, resembling those of RS and OMOD2 patients, indicating that FZD2 mutations are causative. Fzd2em1Smill mutant embryos displayed decreased canonical Wnt signaling in developing limb mesenchyme and disruption of digit chondrocyte elongation and orientation, which is controlled by the \u03b2-catenin-independent WNT5A\/planar cell polarity (PCP) pathway. In line with these observations, we found that disruption of FZD function in limb mesenchyme caused formation of shortened bone elements and defects in Wnt\/\u03b2-catenin and WNT5A\/PCP signaling. These findings indicate that FZD2 controls limb development by mediating both canonical and non-canonical Wnt pathways and reveal causality of pathogenic FZD2 mutations in RS and OMOD2 patients.<\/jats:p>","DOI":"10.1242\/dmm.049876","type":"journal-article","created":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T08:45:41Z","timestamp":1677833141000},"source":"Crossref","is-referenced-by-count":14,"title":["FZD2 regulates limb development by mediating \u03b2-catenin-dependent and -independent Wnt signaling pathways"],"prefix":"10.1242","volume":"16","author":[{"given":"Xuming","family":"Zhu","sequence":"first","affiliation":[{"name":"Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai 1 , New York, NY 10029 , USA"},{"name":"Icahn School of Medicine at Mount Sinai 2 Department of Cell, Developmental and Regenerative Biology , , New York, NY 10029 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingang","family":"Xu","sequence":"additional","affiliation":[{"name":"Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai 1 , New York, NY 10029 , USA"},{"name":"Icahn School of Medicine at Mount Sinai 2 Department of Cell, Developmental and Regenerative Biology , , New York, NY 10029 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. Adrian","family":"Leu","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, University of Pennsylvania 3 Department of Biomedical Sciences , , Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward E.","family":"Morrisey","sequence":"additional","affiliation":[{"name":"University of Pennsylvania 4 Department of Medicine , , Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8792-6890","authenticated-orcid":false,"given":"Sarah E.","family":"Millar","sequence":"additional","affiliation":[{"name":"Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai 1 , New York, NY 10029 , USA"},{"name":"Icahn School of Medicine at Mount Sinai 2 Department of Cell, Developmental and Regenerative Biology , , New York, NY 10029 , USA"},{"name":"Icahn School of Medicine at Mount Sinai 5 Department of Dermatology , , New York, NY 10029 , USA"},{"name":"Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai 6 , New York, NY 10029 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2023,3,24]]},"reference":[{"key":"2023032409255794200_","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1111\/cga.12438","article-title":"Stage-dependent function of Wnt5a during male external genitalia development","volume":"61","author":"Alcantara","year":"2021","journal-title":"Congenit Anom."},{"key":"2023032409255794200_","doi-asserted-by":"publisher","first-page":"e6187","DOI":"10.1002\/ccr3.6187","article-title":"Dominant omodysplasia-A sporadic case-A new case report and review of the literature","volume":"10","author":"Arabzadeh","year":"2022","journal-title":"Clin. 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