Toward understanding SOX9 function in chondrocyte differentiation.
Toward understanding SOX9 function in chondrocyte differentiation.
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DOI：
10.1016/s0945-053x(98)90065-8
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发表时间：
1998-03
期刊：
影响因子：
6.9
通讯作者：
Véronique Lefrebvre;B. Crombrugghe
中科院分区：
文献类型：
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作者：
Véronique Lefrebvre;B. Crombrugghe
触发间充质细胞向软骨细胞分化的决定性转换的转录因子仍然未知。在人类中，SOX9（一种具有与哺乳动物睾丸决定因子SRY相似的dna结合域的转录因子）基因的突变会导致先天性发育不良，这是一种严重的侏儒症综合征，会影响所有软骨来源的结构。在小鼠胚胎发育过程中，Sox9基因在所有软骨前细胞间充质凝聚中变得活跃，并在完全分化的软骨细胞中保持高水平表达。胶原型II （Col2a1）基因中的软骨细胞特异性增强子是软骨细胞的特征标记，是SOX9的直接靶点，在转基因小鼠胚胎中异位表达SOX9足以激活某些组织中的内源性Col2a1基因。这些数据表明SOX9可能在软骨形成中起主要作用。目前正在研究确定软骨细胞中SOX9的其他靶基因，以及其他被认为与SOX9合作激活软骨细胞特异性基因的转录因子。明确SOX9的功能和调控SOX9基因表达的机制有助于更好地理解软骨细胞分化。
The transcription factors that trigger the determinative switch to chondrocyte differentiation in mesenchymal cells are still unknown. In humans, mutations in the gene for SOX9, a transcription factor with a DNA-binding domain similar to that of the mammalian testis-determining factor SRY, cause campomelic dysplasia, a severe dwarfism syndrome which affects all cartilage-derived structures. During mouse embryonic development, the Sox9 gene becomes active in all prechondrocytic mesenchymal condensations, and at later stages its expression is maintained at high levels in fully differentiated chondrocytes. A chondrocyte-specific enhancer in the gene for collagen type II (Col2a1), a characteristic marker of chondrocytes, is a direct target for SOX9, and ectopic expression of SOX9 in transgenic mouse embryos is sufficient to activate the endogenous Col2a1 gene in some tissues. These data suggest that SOX9 could have a major role in chondrogenesis. Studies are in progress to identify other target genes for SOX9 in chondrocytes and also other transcription factors that are believed to cooperate with SOX9 in the activation of chondrocyte-specific genes. Defining SOX9 function and the mechanisms that regulate SOX9 gene expression should contribute to a better understanding of chondrocyte differentiation.