The zinc finger transcription factors Osr1 and Osr2 control synovial joint formation.
The zinc finger transcription factors Osr1 and Osr2 control synovial joint formation.
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DOI：
10.1016/j.ydbio.2011.01.018
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发表时间：
2011-04-01
影响因子：
2.7
通讯作者：
Jiang R
中科院分区：
文献类型：
--
作者：
Gao Y;Lan Y;Liu H;Jiang R
滑膜关节使不同的骨骼元素之间的顺利关节，是必不可少的运动的脊椎动物。尽管对肢体和骨骼发育的分子和细胞机制进行了数十年的广泛研究，但对滑膜关节形成的分子机制仍然知之甚少。特别是，虽然几个信号通路已被证明在关节维护中发挥关键作用，但控制关节启动的机制尚不清楚。在这里，我们报告Osr 1和Osr 2，哺乳动物同源的奇数跳过家庭的锌指转录因子，需要在果蝇腿关节形成，都强烈表达在小鼠的滑膜关节细胞的发展。尽管Osr 1 −/−突变小鼠在妊娠中期死亡，Osr 2 −/−突变小鼠在滑膜关节发育中仅存在轻微缺陷，但Osr 2 −/−突变小鼠发育中肢体间充质中Osr 1的组织特异性失活导致多个关节融合。我们发现Osr 1和Osr 2的功能是维持关节形成关键信号分子表达所必需的，包括Gdf 5，Wnt 4和Wnt 9 b。此外，双突变体中的关节细胞未能上调关节软骨标记基因Prg 4的表达。这些数据表明，Osr 1和Osr 2的功能冗余控制滑膜关节的形成。
Synovial joints enable smooth articulations between different skeletal elements and are essential for the motility of vertebrates. Despite decades of extensive studies of the molecular and cellular mechanisms of limb and skeletal development, the molecular mechanisms governing synovial joint formation are still poorly understood. In particular, whereas several signaling pathways have been shown to play critical roles in joint maintenance, the mechanism controlling joint initiation is unknown. Here we report that Osr1 and Osr2, the mammalian homologs of the odd-skipped family of zinc finger transcription factors that are required for leg joint formation in Drosophila, are both strongly expressed in the developing synovial joint cells in mice. Whereas Osr1−/− mutant mice died at midgestation and Osr2−/− mutant mice had only subtle defects in synovial joint development, tissue-specific inactivation of Osr1 in the developing limb mesenchyme in Osr2−/− mutant mice caused fusion of multiple joints. We found that Osr1 and Osr2 function is required for maintenance of expression of signaling molecules critical for joint formation, including Gdf5, Wnt4 and Wnt9b. In addition, joint cells in the double mutants failed to upregulate expression of the articular cartilage marker gene Prg4. These data indicate that Osr1 and Osr2 function redundantly to control synovial joint formation.
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影响因子：
2.7
作者：
Jiang, RL;Lan, Y;Gridley, T
通讯作者：
Gridley, T
影响因子：
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作者：
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