{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:13:39Z","timestamp":1790356419861,"version":"4.1.0"},"reference-count":63,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,13]],"date-time":"2023-08-13T00:00:00Z","timestamp":1691884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["81873706"],"award-info":[{"award-number":["81873706"]}]},{"name":"National Natural Science Foundation of China","award":["82170912"],"award-info":[{"award-number":["82170912"]}]},{"name":"National Natural Science Foundation of China","award":["2019DCT-M-23"],"award-info":[{"award-number":["2019DCT-M-23"]}]},{"name":"National Natural Science Foundation of China","award":["19-09-02"],"award-info":[{"award-number":["19-09-02"]}]},{"name":"Excellent Talents in Dongcheng District of Beijing","award":["81873706"],"award-info":[{"award-number":["81873706"]}]},{"name":"Excellent Talents in Dongcheng District of Beijing","award":["82170912"],"award-info":[{"award-number":["82170912"]}]},{"name":"Excellent Talents in Dongcheng District of Beijing","award":["2019DCT-M-23"],"award-info":[{"award-number":["2019DCT-M-23"]}]},{"name":"Excellent Talents in Dongcheng District of Beijing","award":["19-09-02"],"award-info":[{"award-number":["19-09-02"]}]},{"name":"Discipline Construction Fund from the Beijing Stomatological Hospital, School of Stomatology, Capital Medical University","award":["81873706"],"award-info":[{"award-number":["81873706"]}]},{"name":"Discipline Construction Fund from the Beijing Stomatological Hospital, School of Stomatology, Capital Medical University","award":["82170912"],"award-info":[{"award-number":["82170912"]}]},{"name":"Discipline Construction Fund from the Beijing Stomatological Hospital, School of Stomatology, Capital Medical University","award":["2019DCT-M-23"],"award-info":[{"award-number":["2019DCT-M-23"]}]},{"name":"Discipline Construction Fund from the Beijing Stomatological Hospital, School of Stomatology, Capital Medical University","award":["19-09-02"],"award-info":[{"award-number":["19-09-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Many processes take place during embryogenesis, and the development of the palate mainly involves proliferation, migration, osteogenesis, and epithelial\u2013mesenchymal transition. Abnormalities in any of these processes can be the cause of cleft palate (CP). There have been few reports on whether C-X-C motif chemokine receptor 4 (CXCR4), which is involved in embryonic development, participates in these processes. In our study, the knockdown of Cxcr4 inhibited the migration of mouse embryonic palatal mesenchymal (MEPM) cells similarly to the use of its inhibitor plerixafor, and the inhibition of cell migration in the Cxcr4 knockdown group was partially reversed by supplementation with\u2002C-X-C motif chemokine ligand 12 (CXCL12). In combination with low-dose retinoic acid (RA), plerixafor increased the incidence of cleft palates in mice by decreasing the expression of Cxcr4 and its downstream migration-regulating gene Rac family small GTPase 1 (RAC1) mediating actin cytoskeleton to affect lamellipodia formation and focal complex assembly and ras homolog family member A (RHOA) regulating the actin cytoskeleton to affect stress fiber formation and focal complex maturation into focal adhesions. Our results indicate that the disruption of cell migration and impaired normal palatal development by inhibition of Cxcr4 expression might be mediated through Rac1 with RhoA. The combination of retinoic acid and plerixafor might increase the incidence of cleft palate, which also provided a rationale to guide the use of the drug during conception.<\/jats:p>","DOI":"10.3390\/ijms241612740","type":"journal-article","created":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T10:13:57Z","timestamp":1692008037000},"page":"12740","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Inhibition of Cxcr4 Disrupts Mouse Embryonic Palatal Mesenchymal Cell Migration and Induces Cleft Palate Occurrence"],"prefix":"10.3390","volume":"24","author":[{"given":"Xiaoyu","family":"Zheng","sequence":"first","affiliation":[{"name":"Laboratory of Orofacial Development, Laboratory of Molecular Signaling and Stem Cells Therapy, Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Tiantan Xili No. 4, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xige","family":"Zhao","sequence":"additional","affiliation":[{"name":"Laboratory of Orofacial Development, Laboratory of Molecular Signaling and Stem Cells Therapy, Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Tiantan Xili No. 4, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijia","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Orofacial Development, Laboratory of Molecular Signaling and Stem Cells Therapy, Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Tiantan Xili No. 4, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[{"name":"Laboratory of Orofacial Development, Laboratory of Molecular Signaling and Stem Cells Therapy, Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Tiantan Xili No. 4, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotong","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Orofacial Development, Laboratory of Molecular Signaling and Stem Cells Therapy, Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Tiantan Xili No. 4, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Peng","sequence":"additional","affiliation":[{"name":"Laboratory of Orofacial Development, Laboratory of Molecular Signaling and Stem Cells Therapy, Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Tiantan Xili No. 4, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Ma","sequence":"additional","affiliation":[{"name":"Laboratory of Orofacial Development, Laboratory of Molecular Signaling and Stem Cells Therapy, Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Tiantan Xili No. 4, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Du","sequence":"additional","affiliation":[{"name":"Laboratory of Orofacial Development, Laboratory of Molecular Signaling and Stem Cells Therapy, Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Tiantan Xili No. 4, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,13]]},"reference":[{"key":"ref_1","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. 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