{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T03:59:44Z","timestamp":1782964784014,"version":"3.54.5"},"reference-count":110,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T00:00:00Z","timestamp":1620604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Riga Stradin\u0161 University (RSU)","award":["5-1\/384\/2020"],"award-info":[{"award-number":["5-1\/384\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Orofacial clefts affect hundreds of thousands of children worldwide annually and are usually corrected by a series of surgeries extending to childhood. The underlying mechanisms that lead to clefts are still unknown, mainly because of the multifactorial etiology and the myriad of interactions between genes and environmental factors. In the present study, we investigated the role and expression of candidate genes belonging to the FGF\/FGFR signaling pathway and FOX family in tissue material obtained from 12 pediatric patients undergoing cleft correction surgery. The expression was investigated using immunohistochemistry (IHC) and chromogenic in-situ hybridization (CISH) in three cell\/tissue types\u2014epithelial cells, connective tissue, and endothelial cells. We found elevated expression of FGFR1 in epithelial cells while no expression was observed in endothelial cells. Further, our results elucidate the potential pathogenetic role of FGFR1 in cellular proliferation, local site inflammation, and fibrosis in cleft patients. Along with bFGF (also called FGF2), FGFR1 could play a pro-inflammatory role in clefts. Over-amplification of FGFR2 in some patients, along with bFGF, could potentially suggest roles for these genes in angiogenesis. Additionally, increased expression of FOXE1 (also called TTF2) contributes to local site inflammation. Finally, zero to low amplification of FOXO1 could suggest its potential role in inducing oxidative stress in the endothelium along with reduced epithelial apoptosis.<\/jats:p>","DOI":"10.3390\/biology10050423","type":"journal-article","created":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T05:30:08Z","timestamp":1620624608000},"page":"423","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Expression Analysis of FGF\/FGFR and FOX Family Proteins in Mucosal Tissue Obtained from Orofacial Cleft-Affected Children"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9804-4666","authenticated-orcid":false,"given":"M\u0101ra","family":"Pilmane","sequence":"first","affiliation":[{"name":"Department of Morphology, Institute of Anatomy and Anthropology, Riga Stradin\u0161 University, LV-1007 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7918-7909","authenticated-orcid":false,"given":"Nityanand","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Morphology, Institute of Anatomy and Anthropology, Riga Stradin\u0161 University, LV-1007 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9650-3504","authenticated-orcid":false,"given":"Zane","family":"Vitenberga-Verza","sequence":"additional","affiliation":[{"name":"Department of Morphology, Institute of Anatomy and Anthropology, Riga Stradin\u0161 University, LV-1007 Riga, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2450","DOI":"10.1001\/jama.299.20.2450-a","article-title":"Grabb and Smith\u2019s plastic surgery","volume":"299","author":"Mathes","year":"2008","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2621","DOI":"10.4103\/jfmpc.jfmpc_472_20","article-title":"Cleft of lip and palate: A review","volume":"9","author":"Vyas","year":"2020","journal-title":"J. Fam. Med. Prim. Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0891-5245(00)70039-3","article-title":"Management of cleft lip and palate in primary care","volume":"14","author":"Mitchell","year":"2000","journal-title":"J. Pediatr. Health Care"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"American Cleft Palate-Craniofacial Association (ACPA) (2018). Parameters for evaluation and treatment of patients with cleft lip\/palate or other craniofacial differences. Cleft Palate Craniofacial J., 55, 137\u2013156.","DOI":"10.1177\/1055665617739564"},{"key":"ref_5","first-page":"45","article-title":"Epidemiology-clinical profile of cleft lip and palate among children in india and its surgical consideration","volume":"2","author":"Banerjee","year":"2013","journal-title":"CIBTech J. Surg."},{"key":"ref_6","first-page":"338","article-title":"Cleft lip and palate: A comprehensive review","volume":"4","author":"Muhamad","year":"2014","journal-title":"Int. J. Basic Appl. Med. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1242\/dev.103.Supplement.41","article-title":"Palate development","volume":"103","author":"Ferguson","year":"1988","journal-title":"Development"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"22174","DOI":"10.1074\/jbc.M113.463620","article-title":"Type 1 fibroblast growth factor receptor in cranial neural crest cell-derived mesenchyme is required for palatogenesis","volume":"288","author":"Wang","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Snyder-Warwick, A.K., and Perlyn, C.A. (2012). Coordinated events: FGF signaling and other related pathways in palatogenesis. J. Craniofacial Surg., 397\u2013400.","DOI":"10.1097\/SCS.0b013e318240fed7"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/35076601","article-title":"Genetics of craniofacial development and malformation","volume":"2","author":"Wilkie","year":"2001","journal-title":"Nat. Rev. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/nrg2933","article-title":"Cleft lip and palate: Understanding genetic and environmental influences","volume":"12","author":"Dixon","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1002\/ajmg.a.32291","article-title":"Rethinking isolated cleft palate: Evidence of occult lip defects in a subset of cases","volume":"146A","author":"Weinberg","year":"2008","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1086\/427344","article-title":"Strong evidence of linkage disequilibrium between polymorphisms at the IRF6 locus and nonsyndromic cleft lip with or without cleft palate, in an Italian population","volume":"76","author":"Scapoli","year":"2005","journal-title":"Am. J. Human Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/ng.506","article-title":"Genome-wide association study identifies two susceptibility loci for nonsyndromic cleft lip with or without cleft palate","volume":"42","author":"Mangold","year":"2010","journal-title":"Nat. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/ng.580","article-title":"A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4","volume":"42","author":"Beaty","year":"2010","journal-title":"Nat. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1136\/jmg.2007.052191","article-title":"Identification of novel candidate genes associated with cleft lip and palate using array comparative genomic hybridisation","volume":"45","author":"Osoegawa","year":"2008","journal-title":"J. Med. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1111\/j.1601-0825.2005.01176.x","article-title":"FGF signalling in craniofacial development and developmental disorders","volume":"12","author":"Nie","year":"2006","journal-title":"Oral. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1002\/ajmg.a.32341","article-title":"Studies of genes in the FGF signaling pathway and oral clefts with or without dental anomalies","volume":"146A","author":"Menezes","year":"2008","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1159\/000224636","article-title":"Genome scan, fine-mapping, and candidate gene analysis of non-syndromic cleft lip with or without cleft palate reveals phenotype-specific differences in linkage and association results","volume":"68","author":"Marazita","year":"2009","journal-title":"Human Hered."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4879","DOI":"10.1093\/hmg\/ddp444","article-title":"FOXE1 association with both isolated cleft lip with or without cleft palate, and isolated cleft palate","volume":"18","author":"Moreno","year":"2009","journal-title":"Human Mol. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/74155","article-title":"MSX1 mutation is associated with orofacial clefting and tooth agenesis in humans","volume":"24","author":"Dorland","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1136\/jmg.40.6.399","article-title":"Complete sequencing shows a role for MSX1 in non-syndromic cleft lip and palate","volume":"40","author":"Jezewski","year":"2003","journal-title":"J. Med. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.ajhg.2009.02.002","article-title":"Mutations in BMP4 are associated with subepithelial, microform, and overt cleft lip","volume":"84","author":"Suzuki","year":"2009","journal-title":"Am. J. Human Genet."},{"key":"ref_24","first-page":"1","article-title":"Structural and functional diversity in the FGF receptor multigene family","volume":"60","author":"Johnson","year":"1993","journal-title":"Adv. Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"14003","DOI":"10.1038\/boneres.2014.3","article-title":"Role of FGF\/FGFR signaling in skeletal development and homeostasis: Learning from mouse models","volume":"2","author":"Su","year":"2014","journal-title":"Bone Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1002\/1096-8628(20000703)93:1<22::AID-AJMG5>3.0.CO;2-U","article-title":"Clinical findings in a patient with FGFR1 P252R mutation and comparison with the literature","volume":"93","author":"Roscioli","year":"2000","journal-title":"Am. J. Med. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1186\/1479-7364-4-5-345","article-title":"Update of human and mouse forkhead box (FOX) gene families","volume":"4","author":"Jackson","year":"2010","journal-title":"Human Genom."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.3889\/oamjms.2019.342","article-title":"Chromogenic in-situ hybridization technique versus immunohistochemistry in assessment of HER2\/neu Status in 448 Iraqi patients with invasive breast carcinoma","volume":"7","author":"Ali","year":"2019","journal-title":"Open Access Maced. J. Med. Sci."},{"key":"ref_29","unstructured":"(2021, March 25). Reliable and Simple Detection of Genomic Alterations Using Light Microscopy. ZytoDotR 2CTM-2-Color CISH for the Detection of Genomic Alterations. A User Manual Provided by ZytoVision GmbH-Fischkai 1, 27572 Bremerhaven- Germany. ZytoVision Molecular Diagnostics Simplified. Available online: www.Zytovision.com."},{"key":"ref_30","first-page":"144","article-title":"Patterns of distribution and occurrence of neuroendocrine elements in lungs of humans with chronic lung disease","volume":"52","author":"Pilmane","year":"1998","journal-title":"Proc. Latv. Acad. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"R68","DOI":"10.1186\/bcr1776","article-title":"Chromogenic in-situ hybridisation for the assessment of HER2 status in breast cancer: An international validation ring study","volume":"9","author":"Bilous","year":"2007","journal-title":"Breast Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1597\/11-132","article-title":"The FGF and FGFR gene family and risk of cleft lip with or without cleft palate","volume":"50","author":"Wang","year":"2013","journal-title":"Cleft Palate Craniofacial J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/j.mod.2007.06.007","article-title":"A dosage-dependent role for Spry2 in growth and patterning during palate development","volume":"124","author":"Welsh","year":"2007","journal-title":"Mech. Dev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e2965","DOI":"10.1038\/cddis.2017.353","article-title":"FGFR1 is critical for the anti-endothelial mesenchymal transition effect of N-acetyl-seryl-aspartyl-lysyl-proline via induction of the MAP4K4 pathway","volume":"8","author":"Li","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"13379","DOI":"10.1073\/pnas.1324235111","article-title":"Endothelial cell FGF signaling is required for injury response but not for vascular homeostasis","volume":"111","author":"Oladipupo","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S0003-9969(02)00204-2","article-title":"Evidence for fibroblast growth factor receptors in myofibroblasts during palatal mucoperiosteal repair","volume":"48","author":"Kanda","year":"2003","journal-title":"Arch. Oral. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1007\/s10753-019-01056-4","article-title":"Inhibition of fibroblast growth factor receptor by AZD4547 protects against inflammation in septic mice","volume":"42","author":"Huang","year":"2019","journal-title":"Inflammation"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"601","DOI":"10.3389\/fcell.2020.00601","article-title":"Disruption of FGF Signaling ameliorates inflammatory response in hepatic stellate cells","volume":"8","author":"Wang","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Pilmane, M., Sidhoma, E., Akota, I., and Kazoka, D. (2019). Characterization of cytokines and proliferation marker Ki67 in cleft affected lip tissue. Medicina (Kaunas), 55.","DOI":"10.3390\/medicina55090518"},{"key":"ref_40","first-page":"187","article-title":"Hypertrophic scarring in cleft lip repair: A comparison of incidence among ethnic groups","volume":"4","author":"Soltani","year":"2012","journal-title":"Clin. Epidemiol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Pilmane, M., Jain, N., Jain, S., Akota, I., and Kroi\u010da, J. (2021). Quantification of cytokines in lip tissue from infants affected by congenital cleft lip and palate. Children (Basel), 8.","DOI":"10.3390\/children8020140"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1172\/JCI20384","article-title":"Disruption of Fgf10\/Fgfr2b-coordinated epithelial-mesenchymal interactions causes cleft palate","volume":"113","author":"Rice","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/jez.b.21274","article-title":"Epithelial-specific requirement of FGFR2 signaling during tooth and palate development","volume":"312B","author":"Hosokawa","year":"2009","journal-title":"J. Exp. Zool. B Mol. Dev. Evol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/nrc2780","article-title":"Fibroblast growth factor signalling: From development to cancer","volume":"10","author":"Turner","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5440","DOI":"10.18632\/oncotarget.6706","article-title":"Expression of the FGFR2 mesenchymal splicing variant in epithelial cells drives epithelial-mesenchymal transition","volume":"7","author":"Ranieri","year":"2016","journal-title":"Oncotarget"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1002\/ijc.29373","article-title":"HPV16 E5 expression induces switching from FGFR2b to FGFR2c and epithelial-mesenchymal transition","volume":"137","author":"Ranieri","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1002\/jcb.240400208","article-title":"Role of growthfactors in inflammation and repair","volume":"40","author":"Wahl","year":"1989","journal-title":"J. Cell Biochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1080\/00016350701884612","article-title":"Effects of bFGF on suppression of collagen type I accumulation and scar tissue formation during wound healing after mucoperiosteal denudation of rat palate","volume":"66","author":"Choi","year":"2008","journal-title":"Acta Odontol. Scand."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1023\/A:1009049932252","article-title":"Endogenous and exogenous fibroblast growth factor-2 modulate wound healing in the chick embryo chorio-allantoic membrane","volume":"3","author":"Ribatti","year":"1999","journal-title":"Angiogenesis"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1210\/endo.135.2.8033826","article-title":"Stimulation of fracture repair by recombinant human basic fibroblast growth factor in normal and streptozotocin-diabetic rats","volume":"135","author":"Kawaguchi","year":"1994","journal-title":"Endocrinology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"18545","DOI":"10.1038\/s41598-020-75584-7","article-title":"Fibroblast growth factor 2 accelerates the epithelial\u2013mesenchymal transition in keratinocytes during wound healing process","volume":"10","author":"Koike","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"835","DOI":"10.2353\/ajpath.2006.050479","article-title":"Basic fibroblast growth factor (bFGF, FGF-2) potentiates leukocyte recruitment to inflammation by enhancing endothelial adhesion molecule expression","volume":"168","author":"Zittermann","year":"2006","journal-title":"Am. J. Pathol."},{"key":"ref_53","first-page":"822","article-title":"VEGF, basic-FGF, and TGF-beta in Crohn\u2019s disease and ulcerative colitis: A novel mechanism of chronic intestinal inflammation","volume":"96","author":"Kanazawa","year":"2001","journal-title":"Am. J. Gastroenterol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"582","DOI":"10.3389\/fnins.2018.00582","article-title":"Inhibitive Effects of FGF2\/FGFR1 Pathway on Astrocyte-Mediated Inflammation in vivo and in vitro After Infrasound Exposure","volume":"12","author":"Shi","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"14839","DOI":"10.1074\/jbc.RA118.002907","article-title":"Ectopic fibroblast growth factor receptor 1 promotes inflammation by promoting nuclear factor-kappaB signaling in prostate cancer cells","volume":"293","author":"Wang","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"32325","DOI":"10.1074\/jbc.M405208200","article-title":"FGF-2 induced by interleukin-1 beta through the action of phosphatidylinositol 3-kinase mediates endothelial mesenchymal transformation in corneal endothelial cells","volume":"279","author":"Lee","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2504","DOI":"10.1172\/JCI116486","article-title":"Interferon-alpha and interleukin 2 synergistically enhance basic fibroblast growth factor synthesis and induce release, promoting endothelial cell growth","volume":"91","author":"Cozzolino","year":"1993","journal-title":"J. Clin. Investig."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4606","DOI":"10.1073\/pnas.92.10.4606","article-title":"Hypoxia-mediated induction of acidic\/basic fibroblast growth factor and platelet-derived growth factor in mononuclear phagocytes stimulates growth of hypoxic endothelial cells","volume":"92","author":"Kuwabara","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1684\/ecn.2009.0155","article-title":"Inflammatory cells and chemokines sustain FGF2-induced angiogenesis","volume":"20","author":"Presta","year":"2009","journal-title":"Eur. Cytokine Netw."},{"key":"ref_60","first-page":"e20170234","article-title":"Assessing the association between hypoxia during craniofacial development and oral clefts","volume":"26","author":"Silva","year":"2018","journal-title":"J. Appl. Oral. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Conte, C., Riant, E., Toutain, C., Pujol, F., Arnal, J.F., Lenfant, F., and Prats, A.C. (2008). FGF2 translationally induced by hypoxia is involved in negative and positive feedback loops with HIF-1alpha. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0003078"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2705","DOI":"10.1182\/blood-2005-09-3541","article-title":"Hypoxic induction of an HIF-1alpha-dependent bFGF autocrine loop drives angiogenesis in human endothelial cells","volume":"107","author":"Calvani","year":"2006","journal-title":"Blood"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1242\/jcs.115.9.1951","article-title":"Increased responsiveness of hypoxic endothelial cells to FGF2 is mediated by HIF-1 alpha-dependent regulation of enzymes involved in synthesis of heparan sulfate FGF2-binding sites","volume":"115","author":"Li","year":"2002","journal-title":"J. Cell Sci."},{"key":"ref_64","first-page":"265","article-title":"The effect of hypoxia on expression of basic fibroblast growth factor in pulmonary vascular pericytes","volume":"20","author":"Wang","year":"2000","journal-title":"J. Tongji Med. Univ."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3318","DOI":"10.1080\/15384101.2015.1087622","article-title":"Binding of FGF2 to FGFR2 in an autocrine mode in trophectoderm cells is indispensable for mouse blastocyst formation through PKC-p38 pathway","volume":"14","author":"Yang","year":"2015","journal-title":"Cell Cycle"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"22190","DOI":"10.1016\/S0021-9258(18)41653-5","article-title":"Interleukin-1-induciblegenes in endothelial cells. Cloning of a new gene related to C-reactive protein and serum amyloid P component","volume":"267","author":"Breviario","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3289","DOI":"10.1182\/blood.V91.9.3289","article-title":"Platelet factor 4 modulates fibroblast growth factor 2 (FGF-2) activity and inhibits FGF-2dimerization","volume":"91","author":"Perollet","year":"1998","journal-title":"Blood"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1002\/dvdy.10118","article-title":"Distribution of the titf2\/foxe1 gene product is consistent with an important role in the development of foregut endoderm, palate, and hair","volume":"224","author":"Dathan","year":"2002","journal-title":"Dev. Dyn."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1093\/hmg\/ddq547","article-title":"MSX1 and TGF-beta3 are novel target genes functionally regulated by FOXE1","volume":"20","author":"Venza","year":"2011","journal-title":"Human Mol Genet."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1034\/j.1600-0544.2002.02227.x","article-title":"Tgf-beta1, Tgf-beta2, Tgf-beta3 and Msx2 expression is elevated during frontonasal suture morphogenesis and during active postnatal facial growth","volume":"5","author":"Adab","year":"2002","journal-title":"Orthod. Craniofacal Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1242\/dev.109.3.585","article-title":"Differential expression of TGF beta isoforms in murine palatogenesis","volume":"109","author":"Fitzpatrick","year":"1990","journal-title":"Development"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez, L.P., L\u00f3pez-M\u00e1rquez, A., Mart\u00ednez, A.M., G\u00f3mez-L\u00f3pez, G., and Santisteban, P. (2013). New insights into FoxE1 functions: Identification of direct FoxE1 targets in thyroid cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0062849"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1089\/scd.2011.0076","article-title":"Nuclear receptors Nur77 and Nurr1 modulate mesenchymal stromal cell migration","volume":"21","author":"Maijenburg","year":"2012","journal-title":"Stem Cells Dev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"85","DOI":"10.3389\/fphys.2012.00085","article-title":"Implications of TGF\u03b2 on transcriptome and cellular biofunctions of palatal mesenchyme","volume":"3","author":"Zhu","year":"2012","journal-title":"Front Physiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2979","DOI":"10.4049\/jimmunol.168.6.2979","article-title":"Activation of nuclear orphan receptor {NURR1} transcription by {NF-kappa} B and cyclic adenosine 5\u2032-monophosphate response element-binding protein in rheumatoid arthritis synovial tissue","volume":"168","author":"McEvoy","year":"2002","journal-title":"J. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s12950-015-0059-2","article-title":"Orphan nuclear receptor NR4A2 induces transcription of the immunomodulatory peptide hormone prolactin","volume":"12","author":"McCoy","year":"2015","journal-title":"J. Inflamm."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"12791","DOI":"10.1038\/srep12791","article-title":"IRF6 is the mediator of TGF\u03b23 during regulation of the epithelial mesenchymal transition and palatal fusion","volume":"5","author":"Ke","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"112310","DOI":"10.1016\/j.yexcr.2020.112310","article-title":"The cleft palate candidate gene BAG6 supports FoxO1 acetylation to\u2006promote FasL-mediated apoptosis during palate fusion","volume":"396","author":"Xu","year":"2020","journal-title":"Exp. Cell Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"19816","DOI":"10.1074\/jbc.M802285200","article-title":"BAT3 interacts with transforming growth factor-beta (TGF-beta) receptors and enhances TGF-beta1-induced type I collagen expression in mesangial cells","volume":"283","author":"Kwak","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/nature16498","article-title":"FOXO1 couples metabolic activity and growth state in the vascular endothelium","volume":"529","author":"Wilhelm","year":"2016","journal-title":"Nature"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1016\/S1079-2104(99)70140-X","article-title":"Salivary gland aplasia with cleft lip and palate: A case report and review of the literature","volume":"87","author":"Matsuda","year":"1999","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1002\/ar.1090860402","article-title":"Multiple congenital anomalies in astillborn infant","volume":"86","author":"Ashley","year":"1943","journal-title":"Anat. Rec."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s10006-009-0182-4","article-title":"Usefulness of fine-needle aspiration in parotid diagnostics","volume":"13","author":"Salgarelli","year":"2009","journal-title":"Oral Maxillofacial Surg."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1002\/dvdy.22786","article-title":"MCS9.7 enhancer activity is highly, but not completely, associated with expression of Irf6 and p63","volume":"241","author":"Fakhouri","year":"2012","journal-title":"Dev. Dyn."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1159\/000342833","article-title":"From the transcription of genes involved in ectodermal dysplasias to the understanding of associated dental anomalies","volume":"3","author":"Langer","year":"2012","journal-title":"Mol. Syndromol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1177\/0022034516679376","article-title":"Massively increased caries susceptibility in an Irf6 cleft lip\/palate model","volume":"96","author":"Tamasas","year":"2017","journal-title":"J. Dent. Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1242\/dev.127.3.483","article-title":"An important role for the IIIb isoform of fibroblast growth factor receptor 2 (FGFR2) in mesenchymal-epithelial signalling during mouse organogenesis","volume":"127","author":"Revest","year":"2000","journal-title":"Development"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1111\/j.1365-2591.2008.01452.x","article-title":"A preliminary study of the use of peripheral quantitative computed tomography for investigating root canal anatomy","volume":"42","author":"Sberna","year":"2009","journal-title":"Int. Endod. J."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Ferrini, F., Sannino, G., Chiola, C., Cappar\u00e9, P., Gastaldi, G., and Gherlone, E.F. (2019). Influence of Intra-Oral Scanner (I.O.S.) on The Marginal Accuracy of CAD\/CAM Single Crowns. Int. J. Environ. Res. Public Health, 16.","DOI":"10.3390\/ijerph16040544"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Cattoni, F., Tet\u00e9, G., Calloni, A.M., Manazza, F., Gastaldi, G., and Cappar\u00e8, P. (2019). Milled versus moulded mock-ups based on the superimposition of 3D meshes from digital oral impressions: A comparative in vitro study in the aesthetic area. BMC Oral Health, 19.","DOI":"10.1186\/s12903-019-0922-2"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Joda, T., Zarone, F., and Ferrari, M. (2017). The complete digital workflow in fixed prosthodontics: A systematic review. BMC Oral Health, 17.","DOI":"10.1186\/s12903-017-0415-0"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1007\/s00784-013-1132-y","article-title":"Accuracy of full-arch scans using intraoral scanners","volume":"18","author":"Patzelt","year":"2014","journal-title":"Clin. Oral Investig."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"384","DOI":"10.11607\/jomi.3303","article-title":"Dental implants in cleft lip, alveolus, and palate patients: A systematic review","volume":"29","author":"Wermker","year":"2014","journal-title":"Int. J. Oral Maxillofac. Implant."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1053\/joms.2001.25852","article-title":"Comprehensive management of cleft lip and palate deformities","volume":"59","author":"Anastassov","year":"2001","journal-title":"J. Oral Maxillofacial Surg."},{"key":"ref_95","first-page":"ic25","article-title":"Cleft lip and palate","volume":"13","author":"Pang","year":"2013","journal-title":"Eplasty"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"231","DOI":"10.3109\/02844311.2010.499666","article-title":"Safety of neonatal cleft lip repair","volume":"44","author":"Harris","year":"2010","journal-title":"J. Plast. Surg. Hand Surg."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1597\/03-028.1","article-title":"Does repairing a cleft lip neonatally have any effect on the longer-term attractiveness of the repair?","volume":"41","author":"Goodacre","year":"2004","journal-title":"Cleft Palate Craniofacial J."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1597\/05-119","article-title":"Hard palate repair timing and facial growth in unilateral cleft lip and palate: A longitudinal study","volume":"43","author":"Liao","year":"2006","journal-title":"Cleft Palate Craniofacial J."},{"key":"ref_99","first-page":"1144","article-title":"Sinus floor elevation by osteotome: Hand mallet versus electric mallet. A prospective clinical study","volume":"27","author":"Crespi","year":"2012","journal-title":"Int. J. Oral Maxillofac. Implant."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1111\/cid.12799","article-title":"Implant survival rate in calvarial bone grafts: A retrospective clinical study with 10 year follow-up","volume":"21","author":"Vinci","year":"2019","journal-title":"Clin. Implant. Dent. Relat. Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1111\/j.1708-8208.2011.00348.x","article-title":"Localized management of sinus floor technique for implant placement in fresh molar sockets","volume":"15","author":"Bruschi","year":"2013","journal-title":"Clin. Implant. Dent. Relat. Res."},{"key":"ref_102","first-page":"991","article-title":"Adult stem cells derived from human maxillary sinus membrane and their osteogenic differentiation","volume":"24","author":"Kim","year":"2009","journal-title":"Int. J. Oral Maxillofac. Implant."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"259","DOI":"10.2174\/1566523220999200818115803","article-title":"The emerging role of stem cells in regenerative dentistry","volume":"20","author":"Sberna","year":"2020","journal-title":"Curr. Gene Ther."},{"key":"ref_104","first-page":"501","article-title":"The \u2018All-on-four\u2019 protocol in HIV-positive patients: A prospective, longitudinal 7-year clinical study","volume":"12","author":"Romanos","year":"2019","journal-title":"Int. J. Oral Implantol. (Berl.)"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1111\/cid.12370","article-title":"A prospective longitudinal study on implant prosthetic rehabilitation in controlled HIV-positive patients with 1-year follow-up: The role of CD4+ level, smoking habits, and oral hygiene","volume":"18","author":"Gherlone","year":"2016","journal-title":"Clin. Implant. Dent. Relat. Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1111\/cid.12353","article-title":"Implant prosthetic rehabilitation in controlled HIV-positive patients: A prospective longitudinal study with 1-year follow-up","volume":"18","author":"Gherlone","year":"2016","journal-title":"Clin. Implant. Dent. Relat. Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1111\/idh.12300","article-title":"The association between three attitude-related indexes of oral hygiene and secondary implant failures: A retrospective longitudinal study","volume":"16","author":"Tecco","year":"2018","journal-title":"Int. J. Dent. Hyg."},{"key":"ref_108","first-page":"49","article-title":"Evaluation of resistance against bacterial microleakage of a new conical implant-abutment connection versus conventional connections: An in vitro study","volume":"39","author":"Gherlone","year":"2016","journal-title":"New Microbiol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"441","DOI":"10.11607\/jomi.3254","article-title":"Radiographic evaluation of crestal bone levels of delayed implants at medium-term follow-up","volume":"29","author":"Bruschi","year":"2014","journal-title":"Int. J. Oral Maxillofac. Implant."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1111\/j.1741-4520.2008.00181.x","article-title":"Morphological and immunohistochemical studies on cleft palates induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice","volume":"48","author":"Fujiwara","year":"2008","journal-title":"Congenit Anom. 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