title: The effect of overexpression of Dlx2 on the migration, proliferation and osteogenic differentiation of cranial neural crest stem cells.
abstract: Craniofacial skeleton mainly originate from the cranial neural crest stem cells (CNCCs), which is a subpopulation of neural crest stem cells (NCCs). Dlx2, a member of the homeodomain family of transcription factors, plays crucial roles in the development of the CNCCs derived craniofacial skeleton. Previous reports reveal that Dlx2-targeted null mutation resulted in anomalies in the skeletal derivatives of CNCCs in mice. Dlx2 overexpression in ova disturbed the migration and differentiation of affected CNCCs and induced the development of ectopic skeleton elements. However, whether Dlx2 overexpression can impair the morphogenesis of CNCCs derived craniofacial skeleton in vivo has not been explored. Here, we generated a transgenic mouse overexpressing Dlx2 in NCCs (Wnt1Cre::iZEG-Dlx2). The Wnt1Cre::iZEG-Dlx2 embryos showed decreased cell proliferation, increased cell apoptosis, abnormal chondrogenesis and impaired osteogenesis within the CNCCs population, resulting in obvious craniofacial defects that ranged from a cleft lip and midfacial clefts to neural tube defects and exencephaly. Adult Wnt1Cre::iZEG-Dlx2 mice showed nasal and premaxillary hypoplasia and spinal deformities. These findings reveal that Dlx2 overexpression in NCCs may be a new pathogenesis of facial cleft and spinal kyphosis in mammals, and may offer us a useful model organism to find suitable therapy methods for these genetic defects that may be different from the traumatic defect and resected defect.
authors.affiliation: Department of Oral & Cranio-maxillofacial Science, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai 200011, China.
authors.forename: Jiewen
authors.initials: J
authors.lastname: Dai
authors.forename: Ying
authors.initials: Y
authors.lastname: Kuang
authors.forename: Bing
authors.initials: B
authors.lastname: Fang
authors.forename: Hui
authors.initials: H
authors.lastname: Gong
authors.forename: Shunyuan
authors.initials: S
authors.lastname: Lu
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Mou
authors.forename: Hao
authors.initials: H
authors.lastname: Sun
authors.forename: Yuefu
authors.initials: Y
authors.lastname: Dong
authors.forename: Jingting
authors.initials: J
authors.lastname: Lu
authors.forename: Wenbin
authors.initials: W
authors.lastname: Zhang
authors.forename: Jianfei
authors.initials: J
authors.lastname: Zhang
authors.forename: Zhugang
authors.initials: Z
authors.lastname: Wang
authors.forename: Xudong
authors.initials: X
authors.lastname: Wang
authors.forename: Guofang
authors.initials: G
authors.lastname: Shen
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D020219:Chondrogenesis; D019465:Craniofacial Abnormalities / Q000196:embryology / Q000235:genetics / Q000473:pathology; D004622:Embryo, Mammalian / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000378:metabolism*; D019426:Integrases / Q000378:metabolism; D008437:Maxilla / Q000378:metabolism / Q000473:pathology; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009432:Neural Crest / Q000166:cytology*; D010012:Osteogenesis; D012886:Skull / Q000166:cytology*; D013131:Spine / Q000002:abnormalities / Q000473:pathology; D013234:Stem Cells / Q000166:cytology*; D014157:Transcription Factors / Q000378:metabolism*; D051153:Wnt Proteins
chemical_list: C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors; D051153:Wnt Proteins; C045073:Cre recombinase; D019426:Integrases