The effect of overexpression of Dlx2 on the migration, proliferation and osteogenic differentiation of cranial neural crest stem cells
The effect of overexpression of Dlx2 on the migration, proliferation and osteogenic differentiation of cranial neural crest stem cells
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Dlx2过表达对颅神经嵴干细胞迁移、增殖及成骨分化的影响
DOI：
10.1016/j.biomaterials.2012.11.051
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发表时间：
2013-03-01
期刊：
影响因子：
14
通讯作者：
Shen, Guofang
中科院分区：
文献类型：
--
作者：
Dai, Jiewen;Kuang, Ying;Shen, Guofang
颅面骨骼主要来源于颅神经嵴干细胞（CNCCs），CNCCs是神经嵴干细胞（NCCs）的一个亚群。Dlx 2是转录因子同源结构域家族的成员，在CNCC源性颅面骨骼发育中起着重要作用。先前的报道显示，Dlx 2靶向的无效突变导致小鼠CNCC骨骼衍生物的异常。Dlx 2在卵细胞中的过表达干扰了受影响的CNCC的迁移和分化，并诱导了异位骨骼元件的发育。然而，Dlx 2过表达是否会损害CNCCs衍生的颅面骨骼在体内的形态发生尚未探讨。在此，我们产生了在NCC中过表达Dlx 2的转基因小鼠（WntlCre：：iZEG-Dlx 2）。Wnt 1Cre：：iZEG-Dlx 2胚胎在CNCC群体中表现出细胞增殖减少、细胞凋亡增加、软骨形成异常和骨形成受损，导致明显的颅面缺陷，从唇裂和面中部裂到神经管缺陷和露脑畸形。成年WntlCre：：iZEG-Dlx 2小鼠显示鼻和前上颌骨发育不全和脊柱畸形。这些结果表明，Dlx 2在NCC中的过表达可能是哺乳动物面裂和脊柱后凸畸形的一种新的发病机制，并可能为我们提供一个有用的模型生物体，以寻找合适的治疗方法，这些遗传缺陷可能不同于创伤性缺陷和切除性缺陷。(C)2012爱思唯尔有限公司保留所有权利。
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 (WntlCre::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 WntlCre::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. (C) 2012 Elsevier Ltd. All rights reserved.