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Mutations in the Arhgap29 gene are significantly associated with non-syndromic cleft lip and palate (NSCL\/P). Our study demonstrated that the deletion of Arhgap29 leads to syndromic cleft lip and palate (SCL\/P) characteristics in mice, where, in addition to cleft palate, the mice exhibit craniofacial and systemic skeletal abnormalities. However, the mechanisms underlying these skeletal abnormalities remain unclear. Through micro-CT imaging, histological analysis, and transcriptomic methods, we discovered that the knockout of Arhgap29 delays the fusion of Meckel\u2019s cartilage, widens cranial sutures, reduces bone quality, and alters the expression of osteoblasts and osteoclasts in the mandible. Digit defects, including ectrodactyly and impaired endochondral ossification, were also observed. Immunohistochemical analysis demonstrated the expression of Arhgap29 in both osteoblasts and osteoclasts, indicating its dual role in maintaining matrix homeostasis and regulating bone resorption equilibrium. Transcriptomic analysis revealed disrupted calcium and MAPK signaling pathways, while in vitro studies demonstrated impaired osteogenesis in Arhgap29-deficient calvarial cells, mirroring the in vivo defects. Furthermore, spatial transcriptomics linked the loss of Arhgap29 to defective bone differentiation and protein synthesis. Our findings underscore the critical role of Arhgap29 in the development of the mandible and digits, suggesting its potential as a pathogenic gene associated with syndromic cleft lip and palate (SCL\/P).<\/jats:p>","DOI":"10.3390\/ijms26104647","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T06:40:23Z","timestamp":1747118423000},"page":"4647","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Arhgap29 Deficiency Directly Leads to Systemic and Craniofacial Skeletal Abnormalities"],"prefix":"10.3390","volume":"26","author":[{"given":"Beibei","family":"Zhang","sequence":"first","affiliation":[{"name":"Ningxia Key Laboratory of Oral Disease Research, Ningxia Key Laboratory of Craniomaxillofacial Deformities Research, School of Stomatology, Ningxia Medical University, Yinchuan 750004, China"},{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Oral Biology, Clinic of Oral Rare and Genetic Diseases, School of Stomatology, The Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyun","family":"Pan","sequence":"additional","affiliation":[{"name":"Ningxia Key Laboratory of Oral Disease Research, Ningxia Key Laboratory of Craniomaxillofacial Deformities Research, School of Stomatology, Ningxia Medical University, Yinchuan 750004, China"},{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Oral Biology, Clinic of Oral Rare and Genetic Diseases, School of Stomatology, The Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Chi","sequence":"additional","affiliation":[{"name":"Ningxia Key Laboratory of Oral Disease Research, Ningxia Key Laboratory of Craniomaxillofacial Deformities Research, School of Stomatology, Ningxia Medical University, Yinchuan 750004, China"},{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Oral Biology, Clinic of Oral Rare and Genetic Diseases, School of Stomatology, The Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Ningxia Key Laboratory of Oral Disease Research, Ningxia Key Laboratory of Craniomaxillofacial Deformities Research, School of Stomatology, Ningxia Medical University, Yinchuan 750004, China"},{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Oral Biology, Clinic of Oral Rare and Genetic Diseases, School of Stomatology, The Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyan","family":"Ruan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Oral Biology, Clinic of Oral Rare and Genetic Diseases, School of Stomatology, The Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Ma","sequence":"additional","affiliation":[{"name":"Ningxia Key Laboratory of Oral Disease Research, Ningxia Key Laboratory of Craniomaxillofacial Deformities Research, School of Stomatology, Ningxia Medical University, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6747-1734","authenticated-orcid":false,"given":"Xiaohong","family":"Duan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Oral Biology, Clinic of Oral Rare and Genetic Diseases, School of Stomatology, The Fourth Military Medical University, Xi\u2019an 710032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqing","family":"Huang","sequence":"additional","affiliation":[{"name":"Ningxia Key Laboratory of Oral Disease Research, Ningxia Key Laboratory of Craniomaxillofacial Deformities Research, School of Stomatology, Ningxia Medical University, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1016\/S0140-6736(09)60695-4","article-title":"Cleft lip and palate","volume":"374","author":"Mossey","year":"2009","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9568","DOI":"10.1038\/s41467-024-53634-2","article-title":"High incidence and geographic distribution of cleft palate in Finland are associated with the IRF6 gene","volume":"15","author":"Rahimov","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zhao, Z., Cui, R., Chi, H., Wan, T., Ma, D., Zhang, J., and Cai, M. (2024). A novel IRF6 gene mutation impacting the regulation of TGFbeta2-AS1 in the TGFbeta pathway: A mechanism in the development of Van der Woude syndrome. Front. Genet., 15.","DOI":"10.3389\/fgene.2024.1397410"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.bjps.2025.01.061","article-title":"Cephalometric analyses of the correlation between nasal and maxilla morphology among adult patients with cleft","volume":"103","author":"Ruojing","year":"2025","journal-title":"J. Plast. Reconstr. Aesthet. Surg."},{"key":"ref_5","unstructured":"Young, A., and Spinner, A. (2023). Hemifacial Microsomia. StatPearls, StatPearls Publishing."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kolb, K., Hellinger, J., Kansy, M., Wegwitz, F., Bauerschmitz, G., Emons, G., and Grundker, C. (2020). Influence of Arhgap29 on the Invasion of Mesenchymal-Transformed Breast Cancer Cells. Cells, 9.","DOI":"10.3390\/cells9122616"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41431-024-01727-3","article-title":"Four putative pathogenic Arhgap29 variants in patients with non-syndromic orofacial clefts (NsOFC)","volume":"33","author":"Ranji","year":"2025","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1007\/s00438-022-01919-w","article-title":"Identification of novel susceptibility genes for non-syndromic cleft lip with or without cleft palate using NGS-based multigene panel testing","volume":"297","author":"Dabrowska","year":"2022","journal-title":"Mol. Genet. Genom."},{"key":"ref_9","first-page":"2840","article-title":"Interferon regulatory factor 6 regulates keratinocyte migration","volume":"127","author":"Biggs","year":"2014","journal-title":"J. Cell Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1177\/0022034517726079","article-title":"Arhgap29 Mutation Is Associated with Abnormal Oral Epithelial Adhesions","volume":"96","author":"Paul","year":"2017","journal-title":"J. Dent. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"101404","DOI":"10.1016\/j.gendis.2024.101404","article-title":"Arhgap29 deficiency causes EEC like syndrome in mice","volume":"12","author":"Chi","year":"2024","journal-title":"Genes Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/tera.1420240106","article-title":"Correlation between alterations in Meckel\u2019s cartilage and induction of cleft palate with beta-aminoproprionitrile in the rat","volume":"24","author":"Diewert","year":"1981","journal-title":"Teratology"},{"key":"ref_13","first-page":"227","article-title":"Mandibular growth retardation as a cause of cleft palate in mice homozygous for the chondrodysplasia gene","volume":"38","author":"Seegmiller","year":"1977","journal-title":"J. Embryol. Exp. Morphol."},{"key":"ref_14","unstructured":"Hegde, N., and Singh, A. (2023). Anesthetic Consideration in Pierre Robin Sequence. StatPearls, StatPearls Publishing."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"111972","DOI":"10.1016\/j.isci.2025.111972","article-title":"Fine-tuning of Wnt signaling by RNA surveillance factor Smg5 in the mouse craniofacial development","volume":"28","author":"Zhu","year":"2025","journal-title":"iScience"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1093\/molbev\/msz145","article-title":"Skeletal Mineralization in Association with Type X Collagen Expression Is an Ancestral Feature for Jawed Vertebrates","volume":"36","author":"Simion","year":"2019","journal-title":"Mol. Biol. Evol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.bjoms.2024.04.008","article-title":"Mandibular distraction osteogenesis in children with Pierre Robin sequence: Long-term analysis of teeth and jaw growth","volume":"62","author":"Govaerts","year":"2024","journal-title":"Br. J. Oral. Maxillofac. Surg."},{"key":"ref_18","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_19","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1126\/science.aas9536","article-title":"Spatiotemporal structure of cell fate decisions in murine neural crest","volume":"364","author":"Soldatov","year":"2019","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Di Iorio, E., Bonelli, F., Bievel-Radulescu, R., Decastello, N., Ferrari, S., Barbaro, V., and Ponzin, D. (2023). Ocular Manifestations in Patients Affected by p63-Associated Disorders: Ectrodactyly-Ectodermal Dysplasia-Clefting (EEC) and Ankyloblepharon-Ectodermal Defects-Cleft Lip Palate (AEC) Syndromes. J. Clin. Med., 12.","DOI":"10.3390\/jcm12237377"},{"key":"ref_21","first-page":"943","article-title":"Identification and characterization of ARHGAP27 gene in silico","volume":"14","author":"Katoh","year":"2004","journal-title":"Int. J. Mol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Yeung, C.C., Taylor, S.H., Garva, R., and Holmes, D.F. (2014). Zeef, L.A.; Soininen, R.; Boot-Handford, R.P.; Kadler, K.E. Arhgap28 is a RhoGAP that inactivates RhoA and downregulates stress fibers. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0107036"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/BF00174948","article-title":"The membranous skeleton: The role of cell condensations in vertebrate skeletogenesis","volume":"186","author":"Hall","year":"1992","journal-title":"Anat. Embryol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.bone.2015.04.035","article-title":"Bone development","volume":"80","author":"Berendsen","year":"2015","journal-title":"Bone"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"dev190488","DOI":"10.1242\/dev.190488","article-title":"Vessel-derived angiocrine IGF1 promotes Meckel\u2019s cartilage proliferation to drive jaw growth during embryogenesis","volume":"147","author":"Marchant","year":"2020","journal-title":"Development"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/bs.ctdb.2018.12.013","article-title":"Regulatory mechanisms of jaw bone and tooth development","volume":"133","author":"Yuan","year":"2019","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Long, F., and Ornitz, D.M. (2013). Development of the endochondral skeleton. Cold Spring Harb. Perspect. Biol., 5.","DOI":"10.1101\/cshperspect.a008334"},{"key":"ref_28","unstructured":"Henry, J.P., and Bordoni, B. (2023). Histology, Osteoblasts. StatPearls, StatPearls Publishing."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Svandova, E., Anthwal, N., Tucker, A.S., and Matalova, E. (2020). Diverse Fate of an Enigmatic Structure: 200 Years of Meckel\u2019s Cartilage. Front. Cell. Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00821"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.ydbio.2008.03.046","article-title":"TGF-beta mediated Dlx5 signaling plays a crucial role in osteo-chondroprogenitor cell lineage determination during mandible development","volume":"321","author":"Oka","year":"2008","journal-title":"Dev. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1196\/annals.1365.035","article-title":"Androulakis, I.I. Bone remodeling","volume":"1092","author":"Hadjidakis","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Florencio-Silva, R., Sasso, G.R.D.S., Sasso-Cerri, E., Simoes, M.J., and Cerri, P.S. (2015). Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells. Biomed. Res. Int., 2015.","DOI":"10.1155\/2015\/421746"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jtbi.2014.01.004","article-title":"Modelling the coupling between intracellular calcium release and the cell cycle during cortical brain development","volume":"347","author":"Barrack","year":"2014","journal-title":"J. Theor. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kito, H., and Ohya, S. (2021). Role of K+ and Ca2+-Permeable Channels in Osteoblast Functions. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910459"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.devcel.2006.04.006","article-title":"Calcineurin\/NFAT signaling in osteoblasts regulates bone mass","volume":"10","author":"Winslow","year":"2006","journal-title":"Dev. Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6861","DOI":"10.1074\/jbc.RA119.011029","article-title":"Calreticulin regulates a switch between osteoblast and chondrocyte lineages derived from murine embryonic stem cells","volume":"295","author":"Pilquil","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1002\/ijc.24392","article-title":"Gene expression profiling of alpha-radiation-induced rat osteosarcomas: Identification of dysregulated genes involved in radiation-induced tumorigenesis of bone","volume":"125","author":"Daino","year":"2009","journal-title":"Int. J. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.jfma.2013.09.015","article-title":"A mutation of the Col2a1 gene (G1170S) alters the transgenic murine phenotype and cartilage matrix homeostasis","volume":"113","author":"Yang","year":"2014","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.bbadis.2013.11.010","article-title":"Ribosome biogenesis in skeletal development and the pathogenesis of skeletal disorders","volume":"1842","author":"Trainor","year":"2014","journal-title":"Biochim Biophys Acta"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Venturi, G., and Montanaro, L. (2020). How Altered Ribosome Production Can Cause or Contribute to Human Disease: The Spectrum of Ribosomopathies. Cells, 9.","DOI":"10.3390\/cells9102300"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3464","DOI":"10.1111\/febs.14622","article-title":"The ribosome biogenesis protein Esf1 is essential for pharyngeal cartilage formation in zebrafish","volume":"285","author":"Chen","year":"2018","journal-title":"FEBS J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.bbrc.2012.05.039","article-title":"Wnt5a signaling is a substantial constituent in bone morphogenetic protein-2-mediated osteoblastogenesis","volume":"422","author":"Nemoto","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1002\/jbmr.79","article-title":"TAK1 regulates cartilage and joint development via the MAPK and BMP signaling pathways","volume":"25","author":"Gunnell","year":"2010","journal-title":"J. Bone. Miner. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1002\/jbmr.2762","article-title":"Suppression of p38alpha MAPK Signaling in Osteoblast Lineage Cells Impairs Bone Anabolic Action of Parathyroid Hormone","volume":"31","author":"Thouverey","year":"2016","journal-title":"J. Bone. Miner. Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"AlMuraikhi, N., Binhamdan, S., Alaskar, H., Alotaibi, A., Tareen, S., Muthurangan, M., and Alfayez, M. (2023). Inhibition of GSK-3beta Enhances Osteoblast Differentiation of Human Mesenchymal Stem Cells through Wnt Signalling Overexpressing Runx2. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24087164"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Miao, K.Z., Cozzone, A., Caetano-Lopes, J., Harris, M.P., and Fisher, S. (2022). Osteoclast activity sculpts craniofacial form to permit sensorineural patterning in the zebrafish skull. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.969481"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/10\/4647\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:31:46Z","timestamp":1760031106000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/10\/4647"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,13]]},"references-count":46,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["ijms26104647"],"URL":"https:\/\/doi.org\/10.3390\/ijms26104647","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,13]]}}}