{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T15:29:38Z","timestamp":1788881378339,"version":"build-2803163510"},"reference-count":95,"publisher":"The Company of Biologists","issue":"6","license":[{"start":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T00:00:00Z","timestamp":1720137600000},"content-version":"vor","delay-in-days":34,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["PJT-166182"],"award-info":[{"award-number":["PJT-166182"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Robinow syndrome is a rare disease caused by variants of seven WNT pathway genes. Craniofacial features include widening of the nasal bridge and jaw hypoplasia. We used the chicken embryo to test whether two missense human FZD2 variants (1301G&amp;gt;T, p.Gly434Val; 425C&amp;gt;T, p.Pro142Lys) were sufficient to change frontonasal mass development. In vivo, the overexpression of retroviruses with wild-type or variant human FZD2 inhibited upper beak ossification. In primary cultures, wild-type and variant human FZD2 significantly inhibited chondrogenesis, with the 425C&amp;gt;T variant significantly decreasing activity of a SOX9 luciferase reporter compared to that for the wild type or 1301G&amp;gt;T. Both variants also increased nuclear shuttling of \u03b2-catenin (CTNNB1) and increased the expression of TWIST1, which are inhibitory to chondrogenesis. In canonical WNT luciferase assays using frontonasal mass cells, the variants had dominant-negative effects on wild-type FZD2. In non-canonical assays, the 425C&amp;gt;T variant failed to activate the reporter above control levels and was unresponsive to exogenous WNT5A. This is the first single amino acid change to selectively alter ligand binding in a FZD receptor. Therefore, FZD2 missense variants are pathogenic and could lead to the altered craniofacial morphogenesis seen in Robinow syndrome.<\/jats:p>","DOI":"10.1242\/dmm.050584","type":"journal-article","created":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T09:58:15Z","timestamp":1720173495000},"source":"Crossref","is-referenced-by-count":9,"title":["Craniofacial studies in chicken embryos confirm the pathogenicity of human <i>FZD2<\/i> variants associated with Robinow syndrome"],"prefix":"10.1242","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8250-8267","authenticated-orcid":false,"given":"Shruti S.","family":"Tophkhane","sequence":"first","affiliation":[{"name":"University of British Columbia 1 Life Sciences Institute and Faculty of Dentistry , , Vancouver, BC V6T 1Z3 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Fu","sequence":"additional","affiliation":[{"name":"University of British Columbia 1 Life Sciences Institute and Faculty of Dentistry , , Vancouver, BC V6T 1Z3 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9795-5094","authenticated-orcid":false,"given":"Esther M.","family":"Verheyen","sequence":"additional","affiliation":[{"name":"Centre for Cell Biology, Development and Disease, Simon Fraser University 2 Department of Molecular Biology and Biochemistry , , Burnaby, BC V5A 1S6 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1409-8163","authenticated-orcid":false,"given":"Joy M.","family":"Richman","sequence":"additional","affiliation":[{"name":"University of British Columbia 1 Life Sciences Institute and Faculty of Dentistry , , Vancouver, BC V6T 1Z3 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2024,7,5]]},"reference":[{"key":"2024070509574556600_DMM050584C1","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1387\/ijdb.170321ja","article-title":"Craniofacial development: discoveries made in the chicken embryo","volume":"62","author":"Abramyan","year":"2018","journal-title":"Int. J. Dev. Biol."},{"key":"2024070509574556600_DMM050584C2","doi-asserted-by":"publisher","first-page":"3584","DOI":"10.1002\/ajmg.a.61884","article-title":"Extremity anomalies associated with Robinow syndrome","volume":"185","author":"Abu-Ghname","year":"2021","journal-title":"Am. J. Med. Genet. A"},{"key":"2024070509574556600_DMM050584C3","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1101\/gad.1171104","article-title":"Interactions between Sox9 and \u03b2-catenin control chondrocyte differentiation","volume":"18","author":"Akiyama","year":"2004","journal-title":"Genes Dev."},{"key":"2024070509574556600_DMM050584C4","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1038\/nrm2717","article-title":"Proximal events in Wnt signal transduction","volume":"10","author":"Angers","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2024070509574556600_DMM050584C5","doi-asserted-by":"publisher","first-page":"886","DOI":"10.3390\/genes11080886","article-title":"Nuclear regulation of Wnt\/beta-catenin signaling: it's a complex situation","volume":"11","author":"Anthony","year":"2020","journal-title":"Genes (Basel)"},{"key":"2024070509574556600_DMM050584C94","doi-asserted-by":"publisher","first-page":"2726","DOI":"10.1002\/ar.24603","article-title":"Development of the chicken skull: A complement to the external staging table of Hamburger and Hamilton","volume":"304","author":"Arnaout","year":"2021","journal-title":"Anat. Rec. (Hoboken)"},{"key":"2024070509574556600_DMM050584C6","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1111\/j.1399-0004.2011.01683.x","article-title":"Craniofacial and intraoral phenotype of Robinow syndrome forms","volume":"80","author":"Beiraghi","year":"2011","journal-title":"Clin. Genet."},{"key":"2024070509574556600_DMM050584C7","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1038\/ng0697-174","article-title":"SOX9 directly regulates the type-II collagen gene","volume":"16","author":"Bell","year":"1997","journal-title":"Nat. Genet."},{"key":"2024070509574556600_DMM050584C8","doi-asserted-by":"publisher","first-page":"W209","DOI":"10.1093\/nar\/gks396","article-title":"RF-Cloning.org: an online tool for the design of restriction-free cloning projects","volume":"40","author":"Bond","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"2024070509574556600_DMM050584C9","doi-asserted-by":"publisher","first-page":"a007906","DOI":"10.1101\/cshperspect.a007906","article-title":"TCF\/LEFs and Wnt signaling in the nucleus","volume":"4","author":"Cadigan","year":"2012","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"2024070509574556600_DMM050584C10","doi-asserted-by":"publisher","first-page":"2541","DOI":"10.1242\/jcs.00451","article-title":"Frizzled receptor dimerization is sufficient to activate the Wnt\/\u03b2-catenin pathway","volume":"116","author":"Carron","year":"2003","journal-title":"J. Cell Sci."},{"key":"2024070509574556600_DMM050584C11","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.mod.2013.02.002","article-title":"Hoxa-5 acts in segmented somites to regulate cervical vertebral morphology","volume":"130","author":"Chen","year":"2013","journal-title":"Mech. Dev."},{"key":"2024070509574556600_DMM050584C12","doi-asserted-by":"publisher","first-page":"3606","DOI":"10.1002\/ajmg.a.61986","article-title":"Craniofacial phenotypes associated with Robinow syndrome","volume":"185","author":"Conlon","year":"2021","journal-title":"Am. J. Med. Genet. A"},{"key":"2024070509574556600_DMM050584C13","doi-asserted-by":"publisher","first-page":"dev193755","DOI":"10.1242\/dev.193755","article-title":"Symmetry and fluctuation of cell movements in neural crest-derived facial mesenchyme","volume":"148","author":"Danescu","year":"2021","journal-title":"Development"},{"key":"2024070509574556600_DMM050584C14","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1038\/35083601","article-title":"Insights into Wnt binding and signalling from the structures of two Frizzled cysteine-rich domains","volume":"412","author":"Dann","year":"2001","journal-title":"Nature"},{"key":"2024070509574556600_DMM050584C15","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1016\/j.devcel.2005.03.016","article-title":"Wnt\/\u03b2-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis","volume":"8","author":"Day","year":"2005","journal-title":"Dev. Cell"},{"key":"2024070509574556600_DMM050584C16","first-page":"162","article-title":"Growth and morphogenesis of the human embryonic midface during primary palate formation analyzed in frontal sections","volume":"13","author":"Diewert","year":"1993","journal-title":"J. Craniofac. Genet. Dev. Biol."},{"key":"2024070509574556600_DMM050584C17","doi-asserted-by":"publisher","first-page":"6789","DOI":"10.1074\/jbc.M114.612648","article-title":"Systematic mapping of WNT-FZD protein interactions reveals functional selectivity by distinct WNT-FZD pairs","volume":"290","author":"Dijksterhuis","year":"2015","journal-title":"J. Biol. Chem."},{"key":"2024070509574556600_DMM050584C18","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1016\/S0165-022X(01)00213-5","article-title":"The FLAG\u2122 peptide, a versatile fusion tag for the purification of recombinant proteins","volume":"49","author":"Einhauer","year":"2001","journal-title":"J. Biochem. Biophys. Methods"},{"key":"2024070509574556600_DMM050584C19","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1016\/j.bbrc.2010.08.074","article-title":"Wnt5a\/Ror2-induced upregulation of xPAPC requires xShcA","volume":"400","author":"Feike","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2024070509574556600_DMM050584C20","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1002\/dvdy.21934","article-title":"Expression of WNT signalling pathway genes during chicken craniofacial development","volume":"238","author":"Geetha-Loganathan","year":"2009","journal-title":"Dev. Dyn."},{"key":"2024070509574556600_DMM050584C21","doi-asserted-by":"publisher","first-page":"24153","DOI":"10.1074\/jbc.M113.522003","article-title":"Avian facial morphogenesis is regulated by c-Jun N-terminal kinase\/planar cell polarity (JNK\/PCP) wingless-related (WNT) signaling","volume":"289","author":"Geetha-Loganathan","year":"2014","journal-title":"J. Biol. Chem."},{"key":"2024070509574556600_DMM050584C22","doi-asserted-by":"publisher","first-page":"2395","DOI":"10.1093\/hmg\/ddz071","article-title":"Robinow syndrome skeletal phenotypes caused by the WNT5AC83S variant are due to dominant interference with chondrogenesis","volume":"28","author":"Gignac","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"2024070509574556600_DMM050584C23","doi-asserted-by":"publisher","first-page":"dmm049844","DOI":"10.1242\/dmm.049844","article-title":"Mechanistic studies in Drosophila and chicken give new insights into functions of DVL1 in dominant Robinow syndrome","volume":"16","author":"Gignac","year":"2023","journal-title":"Dis. Model. Mech."},{"key":"2024070509574556600_DMM050584C24","doi-asserted-by":"publisher","first-page":"4428","DOI":"10.1242\/dev.081679","article-title":"Twist1 mediates repression of chondrogenesis by \u03b2-catenin to promote cranial bone progenitor specification","volume":"139","author":"Goodnough","year":"2012","journal-title":"Development"},{"key":"2024070509574556600_DMM050584C25","doi-asserted-by":"publisher","first-page":"22429","DOI":"10.1074\/jbc.R600015200","article-title":"Wnt signaling: multiple pathways, multiple receptors, and multiple transcription factors","volume":"281","author":"Gordon","year":"2006","journal-title":"J. Biol. Chem."},{"key":"2024070509574556600_DMM050584C26","doi-asserted-by":"publisher","first-page":"a009175","DOI":"10.1101\/cshperspect.a009175","article-title":"The role of Ryk and Ror receptor tyrosine kinases in Wnt signal transduction","volume":"6","author":"Green","year":"2014","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"2024070509574556600_DMM050584C27","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1101\/gad.1022203","article-title":"Coactivation of Rac and Rho by Wnt\/Frizzled signaling is required for vertebrate gastrulation","volume":"17","author":"Habas","year":"2003","journal-title":"Genes Dev."},{"key":"2024070509574556600_DMM050584C28","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1002\/jmor.1050880104","article-title":"A series of normal stages in the development of the chick embryo","volume":"88","author":"Hamburger","year":"1951","journal-title":"J. Morphol."},{"key":"2024070509574556600_DMM050584C29","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1002\/aja.1001950404","article-title":"A series of normal stages in the development of the chick embryo","volume":"195","author":"Hamburger","year":"1992","journal-title":"Dev. Dyn."},{"key":"2024070509574556600_DMM050584C30","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.matbio.2013.02.005","article-title":"Dual functions for WNT5A during cartilage development and in disease","volume":"32","author":"Hosseini-Farahabadi","year":"2013","journal-title":"Matrix Biol."},{"key":"2024070509574556600_DMM050584C31","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1177\/0022034517716916","article-title":"Abnormal WNT5A signaling causes mandibular hypoplasia in Robinow syndrome","volume":"96","author":"Hosseini-Farahabadi","year":"2017","journal-title":"J. Dent. Res."},{"key":"2024070509574556600_DMM050584C32","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1186\/gb-2004-5-7-234","article-title":"The Frizzled family: receptors for multiple signal transduction pathways","volume":"5","author":"Huang","year":"2004","journal-title":"Genome Biol."},{"key":"2024070509574556600_DMM050584C33","first-page":"107","article-title":"The RCAS vector system","volume":"50","author":"Hughes","year":"2004","journal-title":"Folia Biol. (Praha)"},{"key":"2024070509574556600_DMM050584C34","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1002\/dvdy.22009","article-title":"Crosstalk between Wnt and bone morphogenic protein signaling: a turbulent relationship","volume":"239","author":"Itasaki","year":"2010","journal-title":"Dev. Dyn."},{"key":"2024070509574556600_DMM050584C35","doi-asserted-by":"publisher","first-page":"2324709620911771","DOI":"10.1177\/2324709620911771","article-title":"Tomographic study of the malformation complex in correlation with the genotype in patients with Robinow syndrome: review article","volume":"8","author":"Kaissi","year":"2020","journal-title":"J. Investig. Med. High. Impact Case Rep."},{"key":"2024070509574556600_DMM050584C36","doi-asserted-by":"publisher","first-page":"68","DOI":"10.4161\/org.4.2.5851","article-title":"Wnt signal transduction pathways","volume":"4","author":"Komiya","year":"2008","journal-title":"Organogenesis"},{"key":"2024070509574556600_DMM050584C37","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1007\/164_2021_534","article-title":"Employing genetically encoded, biophysical sensors to understand WNT\/frizzled interaction and receptor complex activation","volume":"269","author":"Kozielewicz","year":"2021","journal-title":"Handb. Exp. Pharmacol."},{"key":"2024070509574556600_DMM050584C38","doi-asserted-by":"publisher","first-page":"dev201038","DOI":"10.1242\/dev.201038","article-title":"Successful therapeutic intervention in new mouse models of frizzled 2-associated congenital malformations","volume":"150","author":"Liegel","year":"2023","journal-title":"Development"},{"key":"2024070509574556600_DMM050584C39","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1002\/humu.24375","article-title":"Phenotypic and mutational spectrum of ROR2-related Robinow syndrome","volume":"43","author":"Lima","year":"2022","journal-title":"Hum. Mutat."},{"key":"2024070509574556600_DMM050584C40","doi-asserted-by":"publisher","first-page":"3491","DOI":"10.1002\/jcb.23287","article-title":"Integration of BMP, Wnt, and notch signaling pathways in osteoblast differentiation","volume":"112","author":"Lin","year":"2011","journal-title":"J. Cell. Biochem."},{"key":"2024070509574556600_DMM050584C41","doi-asserted-by":"publisher","first-page":"3050","DOI":"10.1210\/me.2007-0323","article-title":"Homodimerization of Ror2 tyrosine kinase receptor induces 14-3-3(beta) phosphorylation and promotes osteoblast differentiation and bone formation","volume":"21","author":"Liu","year":"2007","journal-title":"Mol. Endocrinol."},{"key":"2024070509574556600_DMM050584C42","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1002\/jcb.21848","article-title":"Wnt5a induces homodimerization and activation of Ror2 receptor tyrosine kinase","volume":"105","author":"Liu","year":"2008","journal-title":"J. Cell. Biochem."},{"key":"2024070509574556600_DMM050584C43","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1093\/dnares\/8.5.221","article-title":"Generation of RCAS vectors useful for functional genomic analyses","volume":"8","author":"Loftus","year":"2001","journal-title":"DNA Res."},{"key":"2024070509574556600_DMM050584C44","doi-asserted-by":"publisher","first-page":"10840","DOI":"10.3390\/ijms221910840","article-title":"Roles of non-canonical Wnt signalling pathways in bone biology","volume":"22","author":"Lojk","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"2024070509574556600_DMM050584C45","doi-asserted-by":"publisher","first-page":"2005","DOI":"10.1002\/ajmg.a.61756","article-title":"50 years of Robinow syndrome","volume":"182","author":"Mazzeu","year":"2020","journal-title":"Am. J. Med. Genet. A."},{"key":"2024070509574556600_DMM050584C46","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1002\/ajmg.a.31592","article-title":"Clinical characterization of autosomal dominant and recessive variants of Robinow syndrome","volume":"143A","author":"Mazzeu","year":"2007","journal-title":"Am. J. Med. Genet. A"},{"key":"2024070509574556600_DMM050584C47","doi-asserted-by":"publisher","first-page":"30167","DOI":"10.1074\/jbc.M109.041715","article-title":"Ror2 receptor requires tyrosine kinase activity to mediate Wnt5A signaling","volume":"284","author":"Mikels","year":"2009","journal-title":"J. Biol. Chem."},{"key":"2024070509574556600_DMM050584C48","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1002\/ajmg.a.38623","article-title":"Nonsense mutations in FZD2 cause autosomal-dominant omodysplasia: Robinow syndrome-like phenotypes","volume":"176","author":"Nagasaki","year":"2018","journal-title":"Am. J. Med. Genet. A"},{"key":"2024070509574556600_DMM050584C49","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1006\/dbio.1996.8487","article-title":"SOX9 binds DNA, activates transcription, and coexpresses with type II collagen during chondrogenesis in the mouse","volume":"183","author":"Ng","year":"1997","journal-title":"Dev. Biol."},{"key":"2024070509574556600_DMM050584C50","doi-asserted-by":"publisher","first-page":"3610","DOI":"10.1128\/MCB.00177-10","article-title":"Ror2\/Frizzled complex mediates Wnt5a-induced AP-1 activation by regulating Dishevelled polymerization","volume":"30","author":"Nishita","year":"2010","journal-title":"Mol. Cell. Biol."},{"key":"2024070509574556600_DMM050584C51","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1016\/j.cell.2017.05.016","article-title":"Wnt\/\u03b2-catenin signaling, disease, and emerging therapeutic modalities","volume":"169","author":"Nusse","year":"2017","journal-title":"Cell"},{"key":"2024070509574556600_DMM050584C52","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1002\/dvdy.22500","article-title":"An ATF2-based luciferase reporter to monitor non-canonical Wnt signaling in Xenopus embryos","volume":"240","author":"Ohkawara","year":"2011","journal-title":"Dev. Dyn."},{"key":"2024070509574556600_DMM050584C53","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1046\/j.1365-2443.2003.00662.x","article-title":"The receptor tyrosine kinase Ror2 is involved in non\u2013canonical Wnt5a\/JNK signalling pathway","volume":"8","author":"Oishi","year":"2003","journal-title":"Genes Cells"},{"key":"2024070509574556600_DMM050584C54","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1136\/jmg.39.5.305","article-title":"Robinow syndrome","volume":"39","author":"Patton","year":"2002","journal-title":"J. Med. Genet."},{"key":"2024070509574556600_DMM050584C55","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1002\/dvdy.22156","article-title":"WNT5A mutations in patients with autosomal dominant Robinow syndrome","volume":"239","author":"Person","year":"2010","journal-title":"Dev. Dyn."},{"key":"2024070509574556600_DMM050584C56","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1002\/pro.109","article-title":"Sequence requirement and subtype specificity in the high-affinity interaction between human frizzled and dishevelled proteins","volume":"18","author":"Punchihewa","year":"2009","journal-title":"Protein Sci."},{"key":"2024070509574556600_DMM050584C57","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.gendis.2023.01.030","article-title":"Canonical and noncanonical Wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk","volume":"11","author":"Qin","year":"2024","journal-title":"Genes Dis."},{"key":"2024070509574556600_DMM050584C58","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.bone.2017.11.013","article-title":"Crispr-Cas9 engineered osteogenesis imperfecta type V leads to severe skeletal deformities and perinatal lethality in mice","volume":"107","author":"Rauch","year":"2018","journal-title":"Bone"},{"key":"2024070509574556600_DMM050584C59","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1242\/dev.109.2.341","article-title":"Differential growth of facial primordia in chick embryos: responses of facial mesenchyme to basic fibroblast growth factor (bFGF) and serum in micromass culture","volume":"109","author":"Richman","year":"1990","journal-title":"Development"},{"key":"2024070509574556600_DMM050584C60","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/0012-1606(89)90142-5","article-title":"Epithelia are interchangeable between facial primordia of chick embryos and morphogenesis is controlled by the mesenchyme","volume":"136","author":"Richman","year":"1989","journal-title":"Dev. Biol."},{"key":"2024070509574556600_DMM050584C61","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/0012-1606(92)90069-S","article-title":"Epithelial-mesenchymal interactions in the outgrowth of limb buds and facial primordia in chick embryos","volume":"154","author":"Richman","year":"1992","journal-title":"Dev. Biol."},{"key":"2024070509574556600_DMM050584C62","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1146\/annurev-biochem-040320-103615","article-title":"The Wnt pathway: from signaling mechanisms to synthetic modulators","volume":"91","author":"Rim","year":"2022","journal-title":"Annu. Rev. Biochem."},{"key":"2024070509574556600_DMM050584C63","doi-asserted-by":"publisher","first-page":"105350","DOI":"10.1016\/j.jbc.2023.105350","article-title":"ROR2 homodimerization is sufficient to activate a neuronal Wnt\/calcium signaling pathway","volume":"299","author":"Riquelme","year":"2023","journal-title":"J. Biol. Chem."},{"key":"2024070509574556600_DMM050584C64","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1001\/archpedi.1969.02100030647005","article-title":"A newly recognized dwarfing syndrome","volume":"117","author":"Robinow","year":"1969","journal-title":"Am. J. Dis. Child"},{"key":"2024070509574556600_DMM050584C65","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.semcdb.2021.10.002","article-title":"Vertebrate Wnt5a - At the crossroads of cellular signalling","volume":"125","author":"Rogers","year":"2022","journal-title":"Semin. Cell Dev. Biol."},{"key":"2024070509574556600_DMM050584C66","article-title":"Autosomal dominant Robinow syndrome","volume-title":"GeneReviews\u00ae[Internet]","author":"Roifman","year":"2019"},{"key":"2024070509574556600_DMM050584C67","doi-asserted-by":"publisher","first-page":"3399","DOI":"10.1093\/hmg\/ddv088","article-title":"A mutation in FRIZZLED2 impairs Wnt signaling and causes autosomal dominant omodysplasia","volume":"24","author":"Saal","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"2024070509574556600_DMM050584C68","doi-asserted-by":"publisher","first-page":"3235","DOI":"10.1007\/s00381-021-05087-x","article-title":"Robinow syndrome in a newborn presenting with hydrocephalus and craniosynostosis","volume":"37","author":"Sakamoto","year":"2021","journal-title":"Childs Nerv. Syst."},{"key":"2024070509574556600_DMM050584C69","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative CT method","volume":"3","author":"Schmittgen","year":"2008","journal-title":"Nat. Protoc."},{"key":"2024070509574556600_DMM050584C70","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1124\/pr.110.002931","article-title":"International union of basic and clinical pharmacology. LXXX. The class Frizzled receptors","volume":"62","author":"Schulte","year":"2010","journal-title":"Pharmacol. Rev."},{"key":"2024070509574556600_DMM050584C71","doi-asserted-by":"publisher","first-page":"3576","DOI":"10.1002\/ajmg.a.61854","article-title":"Neurocognitive, adaptive, and psychosocial functioning in individuals with Robinow syndrome","volume":"185","author":"Schwartz","year":"2021","journal-title":"Am. J. Med. Genet. A"},{"key":"2024070509574556600_DMM050584C72","doi-asserted-by":"publisher","first-page":"2632","DOI":"10.1002\/ajmg.a.61843","article-title":"Characterization of the Robinow syndrome skeletal phenotype, bone micro-architecture, and genotype-phenotype correlations with the osteosclerotic form","volume":"182","author":"Shayota","year":"2020","journal-title":"Am. J. Med. Genet. A"},{"key":"2024070509574556600_DMM050584C73","doi-asserted-by":"publisher","first-page":"474","DOI":"10.4103\/0019-5413.43399","article-title":"Robinow syndrome","volume":"42","author":"Suresh","year":"2008","journal-title":"Ind. J. Orthopaedics"},{"key":"2024070509574556600_DMM050584C74","doi-asserted-by":"publisher","first-page":"E812","DOI":"10.1073\/pnas.1114802109","article-title":"Wnt\/\u03b2-catenin signaling requires interaction of the Dishevelled DEP domain and C terminus with a discontinuous motif in Frizzled","volume":"109","author":"Tauriello","year":"2012","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2024070509574556600_DMM050584C75","doi-asserted-by":"publisher","first-page":"18378","DOI":"10.1038\/s41598-020-75375-0","article-title":"Phosphorylation of Connexin36 near the C-terminus switches binding affinities for PDZ-domain and 14-3-3 proteins in vitro","volume":"10","author":"Tetenborg","year":"2020","journal-title":"Sci. Rep."},{"key":"2024070509574556600_DMM050584C76","doi-asserted-by":"publisher","first-page":"255","DOI":"10.4161\/org.7.4.18797","article-title":"Planar cell polarity signaling in craniofacial development","volume":"7","author":"Topczewski","year":"2011","journal-title":"Organogenesis"},{"key":"2024070509574556600_DMM050584C77","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1159\/000479721","article-title":"A novel de novo FZD2 mutation in a patient with autosomal dominant omodysplasia","volume":"8","author":"T\u00fcrkmen","year":"2017","journal-title":"Mol. Syndromol."},{"key":"2024070509574556600_DMM050584C78","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1007\/978-1-62703-989-5_19","article-title":"Analysis of chondrogenesis using micromass cultures of limb mesenchyme","volume":"1130","author":"Underhill","year":"2014","journal-title":"Methods Mol. Biol."},{"key":"2024070509574556600_DMM050584C79","doi-asserted-by":"publisher","first-page":"2714","DOI":"10.1038\/emboj.2012.150","article-title":"The many faces and functions of beta-catenin","volume":"31","author":"Valenta","year":"2012","journal-title":"EMBO J."},{"key":"2024070509574556600_DMM050584C80","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.ydbio.2012.06.020","article-title":"Wnt5a can both activate and repress Wnt\/\u03b2-catenin signaling during mouse embryonic development","volume":"369","author":"van Amerongen","year":"2012","journal-title":"Dev. Biol."},{"key":"2024070509574556600_DMM050584C81","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1016\/S0960-9822(03)00240-9","article-title":"Zebrafish prickle, a modulator of noncanonical Wnt\/Fz signaling, regulates gastrulation movements","volume":"13","author":"Veeman","year":"2003","journal-title":"Curr. Biol."},{"key":"2024070509574556600_DMM050584C82","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/bs.ctdb.2015.11.028","article-title":"Frizzled receptors in development and disease","volume":"117","author":"Wang","year":"2016","journal-title":"Curr. Top. Dev. Biol."},{"key":"2024070509574556600_DMM050584C83","doi-asserted-by":"publisher","first-page":"2252","DOI":"10.1002\/ccr3.1818","article-title":"Two unrelated patients with autosomal dominant omodysplasia and FRIZZLED2 mutations","volume":"6","author":"Warren","year":"2018","journal-title":"Clin. Case Rep."},{"key":"2024070509574556600_DMM050584C95","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1242\/dev.99.3.341","article-title":"Epithelial-mesenchymal interactions in the development of chick facial primordia and the target of retinoid action","volume":"99","author":"Wedden","year":"1987","journal-title":"Development"},{"key":"2024070509574556600_DMM050584C84","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1083\/jcb.200112029","article-title":"Requirement for RAR-mediated gene repression in skeletal progenitor differentiation","volume":"158","author":"Weston","year":"2002","journal-title":"J. Cell Biol."},{"key":"2024070509574556600_DMM050584C85","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1016\/j.ajhg.2015.02.015","article-title":"DVL1 frameshift mutations clustering in the penultimate exon cause autosomal-dominant Robinow syndrome","volume":"96","author":"White","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"2024070509574556600_DMM050584C86","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/j.ajhg.2016.01.005","article-title":"DVL3 alleles resulting in a -1 frameshift of the last exon mediate autosomal-dominant robinow syndrome","volume":"98","author":"White","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"2024070509574556600_DMM050584C87","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.ajhg.2017.10.002","article-title":"WNT signaling perturbations underlie the genetic heterogeneity of Robinow syndrome","volume":"102","author":"White","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"2024070509574556600_DMM050584C88","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1080\/08977190500125746","article-title":"Wnt signaling through canonical and non-canonical pathways: recent progress","volume":"23","author":"Widelitz","year":"2005","journal-title":"Growth Factors"},{"key":"2024070509574556600_DMM050584C89","doi-asserted-by":"publisher","first-page":"3707","DOI":"10.1242\/dev.052001","article-title":"Frizzled 1 and frizzled 2 genes function in palate, ventricular septum and neural tube closure: general implications for tissue fusion processes","volume":"137","author":"Yu","year":"2010","journal-title":"Development"},{"key":"2024070509574556600_DMM050584C90","doi-asserted-by":"publisher","first-page":"4383","DOI":"10.1242\/dev.083352","article-title":"Frizzled 2 and frizzled 7 function redundantly in convergent extension and closure of the ventricular septum and palate: evidence for a network of interacting genes","volume":"139","author":"Yu","year":"2012","journal-title":"Development"},{"key":"2024070509574556600_DMM050584C91","doi-asserted-by":"publisher","first-page":"3593","DOI":"10.1002\/ajmg.a.61908","article-title":"Novel pathogenic genomic variants leading to autosomal dominant and recessive Robinow syndrome","volume":"185","author":"Zhang","year":"2021","journal-title":"Am. J. Med. Genet. A"},{"key":"2024070509574556600_DMM050584C92","doi-asserted-by":"publisher","first-page":"100074","DOI":"10.1016\/j.xhgg.2021.100074","article-title":"Novel pathogenic variants and quantitative phenotypic analyses of Robinow syndrome: WNT signaling perturbation and phenotypic variability","volume":"3","author":"Zhang","year":"2022","journal-title":"HGG Adv."},{"key":"2024070509574556600_DMM050584C93","doi-asserted-by":"publisher","first-page":"dmm049876","DOI":"10.1242\/dmm.049876","article-title":"FZD2 regulates limb development by mediating \u03b2-catenin-dependent and -independent Wnt signaling pathways","volume":"16","author":"Zhu","year":"2023","journal-title":"Dis. Model. Mech."}],"container-title":["Disease Models &amp; Mechanisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.050584\/3537440\/dmm050584.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.050584\/3537440\/dmm050584.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T09:58:22Z","timestamp":1720173502000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dmm\/article\/17\/6\/dmm050584\/359670\/Craniofacial-studies-in-chicken-embryos-confirm"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,1]]},"references-count":95,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6,1]]}},"URL":"https:\/\/doi.org\/10.1242\/dmm.050584","relation":{},"ISSN":["1754-8403","1754-8411"],"issn-type":[{"value":"1754-8403","type":"print"},{"value":"1754-8411","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,1]]},"article-number":"dmm050584"}}