{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T06:27:12Z","timestamp":1772778432400,"version":"3.50.1"},"reference-count":65,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01DE029818-05"],"award-info":[{"award-number":["1R01DE029818-05"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Midfacial hypoplasia is a developmental defect caused by insufficient growth of the nasal placodes and maxillary prominences. While genetic studies in mice have identified key genes involved in midfacial development, the regulation of these genes during craniofacial development remains poorly understood. In this study, we demonstrate that microRNAs, short non-coding RNAs, play a crucial role in regulating genes involved in midfacial development. We identified 224 genes associated with midfacial malformations in mice. Through bioinformatics analyses, we predicted that several microRNAs, specifically miR-129-5p, miR-381-3p, miR-124-3p, miR-136-5p, miR-448-3p, miR-374, miR-96, and miR-882, could regulate the expression of these genes. Among these, we experimentally focused on the top four candidate microRNAs: miR-129-5p, miR-381-3p, miR-124-3p, and miR-136-5p. Our findings revealed that the overexpression of these microRNAs inhibited cell proliferation and osteogenesis in nasal process mesenchymal cells. These microRNAs regulated genes associated with midfacial malformations in a dose-dependent manner. Taken together, our results emphasize the significance of pathogenic microRNA\u2013gene networks in the cause of midfacial malformations.<\/jats:p>","DOI":"10.3390\/cells15050453","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T16:18:45Z","timestamp":1772554725000},"page":"453","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of Genes and microRNAs Associated with Midfacial Hypoplasia in Mice"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3163-8093","authenticated-orcid":false,"given":"Akiko","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4987-592X","authenticated-orcid":false,"given":"Chihiro","family":"Iwaya","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2246-610X","authenticated-orcid":false,"given":"Ashley","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3975-6836","authenticated-orcid":false,"given":"Junichi","family":"Iwata","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA"},{"name":"Department of Diagnostic & Biomedical Sciences, School of Dentistry, The University of Texas Health Science Center at Houston, Houston, TX 77054, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"ref_1","first-page":"233","article-title":"Orbital decompression and infraorbital augmentation for correction of exophthalmos secondary to Cruzon disease","volume":"36","author":"Sanders","year":"1978","journal-title":"J. Oral Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3683","DOI":"10.1007\/s00381-024-06518-1","article-title":"Mystery of the Muenke midface: Spheno-occipital synchondrosis fusion and craniofacial skeletal patterns","volume":"40","author":"Wu","year":"2024","journal-title":"Childs Nerv. Syst."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"E58","DOI":"10.1055\/s-0042-106397","article-title":"Assessment of Midfacial Hypoplasia in Down Syndrome Fetuses\u2014Validity of a Two-Line Approach and Introduction of a Novel Angle (Maxilla-Mandible-Nasion Angle)","volume":"2","author":"Weichert","year":"2016","journal-title":"Ultrasound Int. Open"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1097\/SCS.0000000000007973","article-title":"Cleft Lip and Palate Midfacial Hypoplasia: Criteria to Choose the Treatment","volume":"33","author":"Farina","year":"2022","journal-title":"J. Craniofac. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1016\/j.ijom.2021.01.013","article-title":"Evaluation of facial aesthetics by laypersons in patients undergoing intraoral quadrangular Le Fort II osteotomy compared with conventional Le Fort I osteotomy","volume":"50","author":"Cede","year":"2021","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e614","DOI":"10.1097\/SCS.0000000000006754","article-title":"Three-Dimensional Planning and Surgical Technique for Modified Le Fort I and Le Fort III Osteotomy in Non-Syndromic Patients","volume":"31","author":"Goulart","year":"2020","journal-title":"J. Craniofac. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1097\/SCS.0000000000009487","article-title":"The Effect of Trans-Sutural Distraction Osteogenesis on Nasal Bone, Nasal Septum, and Nasal Airway in the Treatment for Midfacial Hypoplasia in Growing Patients","volume":"34","author":"Bao","year":"2023","journal-title":"J. Craniofac. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/ajpa.23356","article-title":"Body size and allometric variation in facial shape in children","volume":"165","author":"Larson","year":"2018","journal-title":"Am. J. Phys. Anthr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S24","DOI":"10.1089\/fpsam.2021.0301","article-title":"Sex Differences in Adult Facial Three-Dimensional Morphology: Application to Gender-Affirming Facial Surgery","volume":"24","author":"Bannister","year":"2022","journal-title":"Facial Plast. Surg. Aesthet Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Shaffer, J.R., Orlova, E., Lee, M.K., Leslie, E.J., Raffensperger, Z.D., Heike, C.L., Cunningham, M.L., Hecht, J.T., Kau, C.H., and Nidey, N.L. (2016). Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology. PLoS Genet., 12.","DOI":"10.1371\/journal.pgen.1006149"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Liu, C., Lee, M.K., Naqvi, S., Hoskens, H., Liu, D., White, J.D., Indencleef, K., Matthews, H., Eller, R.J., and Li, J. (2021). Genome scans of facial features in East Africans and cross-population comparisons reveal novel associations. PLoS Genet., 17.","DOI":"10.1371\/journal.pgen.1009695"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Roosenboom, J., Indencleef, K., Lee, M.K., Hoskens, H., White, J.D., Liu, D., Hecht, J.T., Wehby, G.L., Moreno, L.M., and Hodges-Simeon, C. (2018). SNPs Associated With Testosterone Levels Influence Human Facial Morphology. Front. Genet., 9.","DOI":"10.3389\/fgene.2018.00497"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1038\/s41467-019-10617-y","article-title":"Facial recognition from DNA using face-to-DNA classifiers","volume":"10","author":"Sero","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_14","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. (1993). FGFR Craniosynostosis Syndromes Overview. GeneReviews((R)), University of Washington."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3143","DOI":"10.1002\/ajmg.a.38495","article-title":"Homozygous indel mutation in CDH11 as the probable cause of Elsahy-Waters syndrome","volume":"173","author":"Taskiran","year":"2017","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1136\/jmedgenet-2016-104215","article-title":"Diagnostic value of exome and whole genome sequencing in craniosynostosis","volume":"54","author":"Miller","year":"2017","journal-title":"J. Med. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1093\/oxfordjournals.jbchem.a122274","article-title":"Refined X-ray structure of the low pH form of ribonuclease T1-2\u2032-guanylic acid complex at 1.9 A resolution","volume":"103","author":"Sugio","year":"1988","journal-title":"J. Biochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/bs.ctdb.2023.12.002","article-title":"Tissues and signals with true organizer properties in craniofacial development","volume":"157","author":"Tophkhane","year":"2024","journal-title":"Curr. Top Dev. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1002\/dvdy.20833","article-title":"Recent advances in craniofacial morphogenesis","volume":"235","author":"Chai","year":"2006","journal-title":"Dev. Dyn."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1002\/dvdy.20646","article-title":"Development of the upper lip: Morphogenetic and molecular mechanisms","volume":"235","author":"Jiang","year":"2006","journal-title":"Dev. Dyn."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1242\/dev.040048","article-title":"Molecular mechanisms of cranial neural crest cell migration and patterning in craniofacial development","volume":"137","author":"Minoux","year":"2010","journal-title":"Development"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e70001","DOI":"10.1111\/cga.70001","article-title":"The role of sonic hedgehog signaling in the oropharyngeal epithelium during jaw development","volume":"65","author":"Takeuchi","year":"2025","journal-title":"Congenit. Anom."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1242\/dev.00397","article-title":"A zone of frontonasal ectoderm regulates patterning and growth in the face","volume":"130","author":"Hu","year":"2003","journal-title":"Development"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/dvg.20710","article-title":"Mechanisms that underlie co-variation of the brain and face","volume":"49","author":"Marcucio","year":"2011","journal-title":"Genesis"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1002\/dvdy.24368","article-title":"Molecular mechanisms of midfacial developmental defects","volume":"245","author":"Suzuki","year":"2016","journal-title":"Dev. Dyn."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"699","DOI":"10.2174\/156652405774641043","article-title":"Craniofacial anomalies: From development to molecular pathogenesis","volume":"5","author":"Rice","year":"2005","journal-title":"Curr. Mol. Med."},{"key":"ref_27","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_28","doi-asserted-by":"crossref","unstructured":"Grzesik-Gasior, J., Bien, A., Zalewska, K., Nieszporek, M., Witkowska, K., and Merklinger-Gruchala, A. (2026). Maternal-Fetal Exposure to Oncoelements and Their Oxidative and Epigenetic Impact on Pregnancy Outcomes. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27020669"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.diff.2022.01.002","article-title":"MicroRNAs as epigenetic regulators of orofacial development","volume":"124","author":"Seelan","year":"2022","journal-title":"Differentiation"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/s41580-024-00805-0","article-title":"The biogenesis and regulation of animal microRNAs","volume":"26","author":"Kim","year":"2025","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"D147","DOI":"10.1093\/nar\/gkae1072","article-title":"miRTarBase 2025: Updates to the collection of experimentally validated microRNA-target interactions","volume":"53","author":"Cui","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"R90","DOI":"10.1186\/gb-2010-11-8-r90","article-title":"Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites","volume":"11","author":"Betel","year":"2010","journal-title":"Genome Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1038\/ng2135","article-title":"The role of site accessibility in microRNA target recognition","volume":"39","author":"Kertesz","year":"2007","journal-title":"Nat. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1101\/gr.082701.108","article-title":"Most mammalian mRNAs are conserved targets of microRNAs","volume":"19","author":"Friedman","year":"2009","journal-title":"Genome Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.molcel.2007.06.017","article-title":"MicroRNA targeting specificity in mammals: Determinants beyond seed pairing","volume":"27","author":"Grimson","year":"2007","journal-title":"Mol. Cell"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Iwaya, C., Suzuki, A., and Iwata, J. (2025). Overexpression of miR-320-3p, miR-381-3p, and miR-27a-3p Suppresses Genes Related to Midline Facial Cleft in Mouse Cranial Neural Crest Cells. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262110730"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Iwaya, C., Yu, S., and Iwata, J. (2024). Genes Related to Frontonasal Malformations Are Regulated by miR-338-5p, miR-653-5p, and miR-374-5p in O9-1 Cells. J. Dev. Biol., 12.","DOI":"10.3390\/jdb12030019"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Iwaya, C., and Iwata, J. (2025). miR-383-3p and miR-6951-3p activate cell proliferation through the regulation of genes related to hypertelorism. Front. Cell Dev. Biol., 13.","DOI":"10.3389\/fcell.2025.1587052"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Iwaya, C., Suzuki, A., Jun, G., and Iwata, J. (2025). miR-302a\/b\/d-3p Differentially Expressed During Frontonasal Development Is Sensitive to Retinoic Acid Exposure. Cells, 14.","DOI":"10.3390\/cells14141068"},{"key":"ref_40","first-page":"2834","article-title":"MicroRNA-129-5p inhibits human glioma cell proliferation and induces cell cycle arrest by directly targeting DNMT3A","volume":"10","author":"Gu","year":"2018","journal-title":"Am. J. Transl. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1038\/s41419-019-1923-4","article-title":"MiR-129-5p inhibits liver cancer growth by targeting calcium calmodulin-dependent protein kinase IV (CAMK4)","volume":"10","author":"Li","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.bbrc.2015.06.108","article-title":"miR-129 suppresses tumor cell growth and invasion by targeting PAK5 in hepatocellular carcinoma","volume":"464","author":"Zhai","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Peng, H., Guo, Q., Xiao, Y., Su, T., Jiang, T.J., Guo, L.J., and Wang, M. (2020). ASPH Regulates Osteogenic Differentiation and Cellular Senescence of BMSCs. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00872"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.bone.2007.06.024","article-title":"Type XXVII collagen at the transition of cartilage to bone during skeletogenesis","volume":"41","author":"Hjorten","year":"2007","journal-title":"Bone"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1002\/jbmr.3305","article-title":"Loss of Dnmt3b in Chondrocytes Leads to Delayed Endochondral Ossification and Fracture Repair","volume":"33","author":"Wang","year":"2018","journal-title":"J. Bone Miner. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5852","DOI":"10.1002\/jcb.26775","article-title":"Ablation of Dnmt3b in chondrocytes suppresses cell maturation during embryonic development","volume":"119","author":"Xu","year":"2018","journal-title":"J. Cell. Biochem."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Lai, Z., Shu, Q., Song, Y., Tang, A., and Tian, J. (2024). Effect of DNA methylation on the osteogenic differentiation of mesenchymal stem cells: Concise review. Front. Genet., 15.","DOI":"10.3389\/fgene.2024.1429844"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e70703","DOI":"10.1111\/jcmm.70703","article-title":"Hypoxia-Driven Regulation of Osteogenic Differentiation in Human Periosteal Stem Cells via the HIF-1alpha\/miR-129-5p\/BMP2 Axis","volume":"29","author":"Lu","year":"2025","journal-title":"J. Cell. Mol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.bbrc.2021.05.072","article-title":"miR-129-5p in exosomes inhibits diabetes-associated osteogenesis in the jaw via targeting FZD4","volume":"566","author":"Wang","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"7435605","DOI":"10.1155\/2021\/7435605","article-title":"miR-129-5p Promotes Osteogenic Differentiation of BMSCs and Bone Regeneration via Repressing Dkk3","volume":"2021","author":"Zhao","year":"2021","journal-title":"Stem Cells Int."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1111\/jre.13060","article-title":"A grooved porous hydroxyapatite scaffold induces osteogenic differentiation via regulation of PKA activity by upregulating miR-129-5p expression","volume":"57","author":"Deng","year":"2022","journal-title":"J. Periodontal Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s10142-022-00950-9","article-title":"Tumor-suppressing effects of miR-381-3p in pediatric acute myeloid leukemia via ROCK1 downregulation","volume":"23","author":"Ye","year":"2023","journal-title":"Funct. Integr. Genom."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/jcb.27438","article-title":"miR-381-3p restrains cervical cancer progression by downregulating FGF7","volume":"120","author":"Shang","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_54","first-page":"913","article-title":"miR-381-3p suppresses the proliferation of oral squamous cell carcinoma cells by directly targeting FGFR2","volume":"7","author":"Yang","year":"2017","journal-title":"Am. J. Cancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1186\/s13018-024-04992-6","article-title":"Mir-381-3p aggravates ovariectomy-induced osteoporosis by inhibiting osteogenic differentiation through targeting KLF5\/Wnt\/beta-catenin signaling pathway","volume":"19","author":"Zhao","year":"2024","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"101791","DOI":"10.1016\/j.tice.2022.101791","article-title":"Effect of miR-381-3p\/FGF7 axis on the osteogenic differentiation of bone marrow mesenchymal stem cells through MEK\/ERK signaling pathway","volume":"76","author":"Qiu","year":"2022","journal-title":"Tissue Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/ijos.2015.14","article-title":"The Hedgehog signalling pathway in bone formation","volume":"7","author":"Yang","year":"2015","journal-title":"Int. J. Oral Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/j.devcel.2008.02.003","article-title":"Hedgehog signaling in mature osteoblasts regulates bone formation and resorption by controlling PTHrP and RANKL expression","volume":"14","author":"Mak","year":"2008","journal-title":"Dev. Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"148265","DOI":"10.1016\/j.gene.2024.148265","article-title":"MiR-136-5p in cancer: Roles, mechanisms, and chemotherapy resistance","volume":"909","author":"Zhang","year":"2024","journal-title":"Gene"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Suzuki, A., Yoshioka, H., Summakia, D., Desai, N.G., Jun, G., Jia, P., Loose, D.S., Ogata, K., Gajera, M.V., and Zhao, Z. (2019). MicroRNA-124-3p suppresses mouse lip mesenchymal cell proliferation through the regulation of genes associated with cleft lip in the mouse. BMC Genom., 20.","DOI":"10.1186\/s12864-019-6238-4"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Gajera, M., Desai, N., Suzuki, A., Li, A., Zhang, M., Jun, G., Jia, P., Zhao, Z., and Iwata, J. (2019). MicroRNA-655-3p and microRNA-497-5p inhibit cell proliferation in cultured human lip cells through the regulation of genes related to human cleft lip. BMC Med. Genom., 12.","DOI":"10.1186\/s12920-019-0535-2"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1002\/dvg.20717","article-title":"Sox9 function in craniofacial development and disease","volume":"49","author":"Lee","year":"2011","journal-title":"Genesis"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"9360","DOI":"10.1073\/pnas.1631288100","article-title":"Sox9 is required for determination of the chondrogenic cell lineage in the cranial neural crest","volume":"100","author":"Akiyama","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1002\/(SICI)1097-0177(199708)209:4<377::AID-AJA5>3.0.CO;2-F","article-title":"Parallel expression of Sox9 and Col2a1 in cells undergoing chondrogenesis","volume":"209","author":"Zhao","year":"1997","journal-title":"Dev. Dyn."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2813","DOI":"10.1101\/gad.1017802","article-title":"The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6","volume":"16","author":"Akiyama","year":"2002","journal-title":"Genes Dev."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/5\/453\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T05:23:55Z","timestamp":1772774635000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/5\/453"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,3]]},"references-count":65,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["cells15050453"],"URL":"https:\/\/doi.org\/10.3390\/cells15050453","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,3]]}}}