Cx43 suppresses evx1 expression to regulate joint initiation in the regenerating fin.

Cx43 suppresses evx1 expression to regulate joint initiation in the regenerating fin.
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DOI:
10.1002/dvdy.24531
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发表时间:
2017-09
期刊:
Developmental dynamics : an official publication of the American Association of Anatomists
影响因子:
--
通讯作者:
Iovine MK
Iovine MK
中科院分区:
其他
文献类型:
--
作者:
Dardis G;Tryon R;Ton Q;Johnson SL;Iovine MK

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关节如何在脊椎动物骨骼中正确定位仍然知之甚少。从我们对再生鳍的研究中,我们有证据表明,差距连接蛋白Cx 43通过抑制evx 1转录因子的表达来抑制关节形成。关节形态发生至少经历两个不连续的阶段。首先,将产生关节的细胞在骨基质上凝聚成单行(“起始”)。第二,这些细胞与骨基质的接合一致地分离。我们建议,Cx43活性是短暂的联合启动前减少。我们首先定义的时间联合启动相对于再生。我们接下来将cx43表达减少和evx1表达增加与启动相关。通过操纵cx43的表达,我们表明,Cx43的负面影响evx1的表达和关节形成。我们进一步证明,Cx43活性在真皮成纤维细胞是需要救援的Cx43突变体,短鳍b123关节形成。我们的结论是,皮肤成纤维细胞中的Cx43活性影响evx1的表达,因此,引起关节形成成骨细胞的前体细胞的分化。
How joints are correctly positioned in the vertebrate skeleton remains poorly understood. From our studies on the regenerating fin, we have evidence that the gap junction protein Cx43 suppresses joint formation by suppressing the expression of the evx1 transcription factor. Joint morphogenesis proceeds through at least two discrete stages. First, cells that will produce the joint condense in a single row on the bone matrix (“initiation”). Second, these cells separate coincident with articulation of the bone matrix. We propose that Cx43 activity is transiently reduced prior to joint initiation. We first define the timing of joint initiation with respect to regeneration. We next correlate reduced cx43 expression and increased evx1 expression with initiation. Through manipulation of cx43 expression we demonstrate that Cx43 negatively influences evx1 expression and joint formation. We further demonstrate that Cx43 activity in the dermal fibroblasts is required to rescue joint formation in the cx43 mutant, short fin b123. We conclude that Cx43 activity in the dermal fibroblasts influences the expression of evx1, and therefore the differentiation of the precursor cells that give rise to the joint-forming osteoblasts.
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