Studies on the role of Cux1 in regulation of the onset of joint formation in the developing limb.
Studies on the role of Cux1 in regulation of the onset of joint formation in the developing limb.
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研究 Cux1 在调节肢体发育中关节形成开始中的作用。
DOI：
10.1006/dbio.2001.0559
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Kosher,RobertA
中科院分区：
文献类型：
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作者：
Lizarraga,Gail;Lichtler,Alexander;Upholt,WilliamB;Kosher,RobertA
关节的形成，其特征在于连续的骨骼雏形分割成两个或多个独立的元素，是肢体模式形成的一个基本方面，在确定单个骨骼元素的大小，形状和数量方面起着关键作用。关节形成是由假定关节部位的分化软骨细胞转化为关节间区密集的非软骨细胞而开始的。这种转化伴随着阿辛蓝染色软骨基质的丢失和软骨特异性基因表达的下调。在这里，我们报告说，Cux1，它编码一个转录因子含有同源结构域和其他DNA结合基序，是高度表达在所有的离散网站的初期关节形成在发展中的肢体伴随着转换分化的软骨细胞到interzone组织。此外，在微团培养物中用Cux1逆转录病毒表达载体感染的分化的肢体软骨细胞被转化成非软骨细胞，其表现出在正常关节形成开始时发生的阿辛蓝软骨基质的损失和软骨特异性基因表达的下调。这些结果表明，Cux1参与调节关节形成的开始，通过促进软骨细胞转化为非软骨细胞的间区。
Joint formation, the onset of which is characterized by the segmentation of continuous skeletal rudiments into two or more separate elements, is a fundamental aspect of limb pattern formation, playing a critical role in determining the size, shape, and number of individual skeletal elements. Joint formation is initiated by conversion of differentiated chondrocytes at sites of presumptive joints into densely packed nonchondrogenic cells of the joint interzone. This conversion is accompanied by loss of Alcian blue-staining cartilage matrix and downregulation of cartilage-specific gene expression. Here, we report that Cux1, which encodes a transcription factor containing a homeodomain and other DNA-binding motifs, is highly expressed at all of the discrete sites of incipient joint formation in the developing limb concomitant with conversion of differentiated chondrocytes into interzone tissue. Moreover, differentiated limb chondrocytes in micromass cultures infected with a Cux1 retroviral expression vector are converted into nonchondrogenic cells which exhibit loss of Alcian blue cartilage matrix and downregulation of cartilage-specific gene expression as occurs at the onset of normal joint formation. These results suggest that Cux1 is involved in regulating the onset of joint formation by facilitating conversion of chondrocytes into nonchondrogenic cells of the interzone.