Fate of the mammalian cranial neural crest during tooth and mandibular morphogenesis.
Fate of the mammalian cranial neural crest during tooth and mandibular morphogenesis.
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发表时间：
2000-04
期刊：
影响因子：
4.6
通讯作者：
Yang Chai;Xiaobing Jiang;Yoshihiro Ito;P. Bringas;Jun Han;David H. Rowitch;Philippe Soriano
中科院分区：
文献类型：
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作者：
Yang Chai;Xiaobing Jiang;Yoshihiro Ito;P. Bringas;Jun Han;David H. Rowitch;Philippe Soriano
神经嵴细胞是一种多潜能干细胞，对脊椎动物的发育有广泛的贡献，并产生各种细胞和组织类型。由于缺乏适当的标记物，哺乳动物神经嵴命运的确定受到抑制。在这里，我们利用双组分遗传系统在牙齿和下颌骨发育过程中不可磨灭地标记颅神经嵴的后代。在第一个小鼠系中，Cre重组酶在Wnt1启动子的控制下作为转基因表达。值得注意的是，Wnt1转基因表达仅限于来自背中枢神经系统的迁移神经嵴细胞。第二个小鼠系，ROSA26条件报告基因（R26R），作为cre介导重组的底物。利用这种双组分遗传系统，我们系统地跟踪了出生后9.5至6周颅神经嵴（CNC）细胞的迁移和分化。我们的研究结果首次证明，CNC细胞有助于凝聚牙间质、牙乳头、成牙细胞、牙本质基质、牙髓、牙骨质、牙周韧带、梅克尔软骨、下颌骨、颞下颌关节盘和鳃弓神经节软骨细胞的形成。更重要的是，在牙齿和下颌的形态发生过程中，CNC和非CNC来源的细胞是动态分布的。这些结果是全面了解哺乳动物颅面发育过程中神经嵴细胞迁移和分化的第一步。此外，该转基因模型还为正常和异常胚胎发生中神经嵴衍生成分的细胞谱系分析和遗传操作提供了新的工具。
Neural crest cells are multipotential stem cells that contribute extensively to vertebrate development and give rise to various cell and tissue types. Determination of the fate of mammalian neural crest has been inhibited by the lack of appropriate markers. Here, we make use of a two-component genetic system for indelibly marking the progeny of the cranial neural crest during tooth and mandible development. In the first mouse line, Cre recombinase is expressed under the control of the Wnt1 promoter as a transgene. Significantly, Wnt1 transgene expression is limited to the migrating neural crest cells that are derived from the dorsal CNS. The second mouse line, the ROSA26 conditional reporter (R26R), serves as a substrate for the Cre-mediated recombination. Using this two-component genetic system, we have systematically followed the migration and differentiation of the cranial neural crest (CNC) cells from E9.5 to 6 weeks after birth. Our results demonstrate, for the first time, that CNC cells contribute to the formation of condensed dental mesenchyme, dental papilla, odontoblasts, dentine matrix, pulp, cementum, periodontal ligaments, chondrocytes in Meckel's cartilage, mandible, the articulating disc of temporomandibular joint and branchial arch nerve ganglia. More importantly, there is a dynamic distribution of CNC- and non-CNC-derived cells during tooth and mandibular morphogenesis. These results are a first step towards a comprehensive understanding of neural crest cell migration and differentiation during mammalian craniofacial development. Furthermore, this transgenic model also provides a new tool for cell lineage analysis and genetic manipulation of neural-crest-derived components in normal and abnormal embryogenesis.