{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T10:48:19Z","timestamp":1789728499079,"version":"4.0.1"},"reference-count":82,"publisher":"The Company of Biologists","issue":"9","license":[{"start":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T00:00:00Z","timestamp":1652313600000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Johns"},{"name":"Hopkins University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>In central nervous system vascular endothelial cells, signaling via the partially redundant ligands WNT7A and WNT7B requires two co-activator proteins, GPR124 and RECK. WNT7A and RECK have been shown previously to play a role in limb development, but the mechanism of RECK action in this context is unknown. The roles of WNT7B and GPR124 in limb development have not been investigated. Using combinations of conventional and\/or conditional loss-of-function alleles for mouse Wnt7a, Wnt7b, Gpr124 and Reck, including a Reck allele that codes for a protein that is specifically defective in WNT7A\/WNT7B signaling, we show that reductions in ligand and\/or co-activator function synergize to cause reduced and dysmorphic limb bone growth. Two additional limb phenotypes \u2013 loss of distal Lmx1b expression and ectopic growth of nail-like structures \u2013 occur with reduced Wnt7a\/Wnt7b gene copy number and, respectively, with Reck mutations and with combined Reck and Gpr124 mutations. A third limb phenotype \u2013 bleeding into a digit \u2013 occurs with the most severe combinations of Wnt7a\/Wnt7b, Reck and Gpr124 mutations. These data imply that the WNT7A\/WNT7B-FRIZZLED-LRP5\/LRP6-GPR124-RECK signaling system functions as an integral unit in limb development.<\/jats:p>","DOI":"10.1242\/dev.200340","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T12:43:06Z","timestamp":1652359386000},"source":"Crossref","is-referenced-by-count":19,"title":["The WNT7A\/WNT7B\/GPR124\/RECK signaling module plays an essential role in mammalian limb development"],"prefix":"10.1242","volume":"149","author":[{"given":"Yanshu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjun","family":"Venkatesh","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip M.","family":"Smallwood","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2002-622X","authenticated-orcid":false,"given":"Aaron","family":"James","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8106-5460","authenticated-orcid":false,"given":"Jeremy","family":"Nathans","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2022,5,12]]},"reference":[{"key":"2022051212384458200_DEV200340C1","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.ydbio.2014.12.031","article-title":"Wnt7b is required for epithelial progenitor growth and operates during epithelial-to-mesenchymal signaling in pancreatic development","volume":"399","author":"Afelik","year":"2015","journal-title":"Dev. 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