Sox9 is required for determination of the chondrogenic cell lineage in the cranial neural crest
Sox9 is required for determination of the chondrogenic cell lineage in the cranial neural crest
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DOI：
10.1073/pnas.1631288100
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发表时间：
2003-08-05
影响因子：
11.1
通讯作者：
de Crombrugghe, B
中科院分区：
文献类型：
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作者：
Mori-Akiyama, Y;Akiyama, H;de Crombrugghe, B
Sox9在轴骨和阑尾骨形成过程中在软骨内骨形成中起重要作用。Sox9也在神经嵴细胞中表达，但其在神经嵴中的功能尚不清楚。由于许多颅面骨骼元件来源于颅神经嵴（CNC）细胞，我们想知道使用Cre重组酶/loxP重组系统删除CNC细胞中的Sox9是否会影响颅面发育。神经嵴中Sox9的失活导致CNC软骨和软骨内骨完全缺失。相比之下，所有的中胚层骨骼元素和膜内骨骼基本上都被保留了下来。Sox9-null突变体CNC细胞的迁移和定位正常。事实上，突变胚胎的鳃弓大小和额鼻质量与WT胚胎相当，并且Ap2的表达模式正常，Ap2是CNC细胞迁移的标志。此外，在小鼠胚胎嵌合体中，Sox9-null突变细胞迁移到它们在软骨内骨骼元件中的正确位置；然而，sox9缺失的CINC细胞不能促进软骨间充质凝聚。在突变胚胎中，在WT胚胎鼻软骨存在的位置发现了Runx2、Osterix和Col1a1等成骨细胞标记基因的异位表达。这些结果表明，Sox9的失活导致CNC细胞失去其软骨形成潜能。我们假设这些细胞改变了它们的细胞命运并获得了向成骨细胞分化的能力。我们得出结论，Sox9是确定CNC细胞中软骨细胞谱系所必需的。
Sox9 has essential roles in endochondral bone formation during axial and appendicular skeletogenesis. Sox9 is also expressed in neural crest cells, but its function in neural crest remains largely unknown. Because many craniofacial skeletal elements are derived from cranial neural crest (CNC) cells, we asked whether deletion of Sox9 in CNC cells by using the Cre recombinase/loxP recombination system would affect craniofacial development. Inactivation of Sox9 in neural crest resulted in a complete absence of cartilages and endochondral bones derived from the CNC. In contrast, all of the mesodermal skeletal elements and intramembranous bones were essentially conserved. The migration and the localization of Sox9-null mutant CNC cells were normal. Indeed, the size of branchial arches and the frontonasal mass of mutant embryos was comparable to that of WT embryos, and the pattern of expression of Ap2, a marker of migrating CNC cells, was normal. Moreover, in mouse embryo chimeras Sox9-null mutant cells migrated to their correct location in endochondral skeletal elements; however, Sox9-null CINC cells were unable to contribute chondrogenic mesenchymal condensations. In mutant embryos, ectopic expression of osteoblast marker genes, such as Runx2, Osterix, and Col1a1, was found in the locations where the nasal cartilages exist in WT embryos. These results indicate that inactivation of Sox9 causes CNC cells to lose their chondrogenic potential. We hypothesize that these cells change their cell fate and acquire the ability to differentiate into osteoblasts. We conclude that Sox9 is required for the determination of the chondrogenic lineage in CNC cells.