Regulation of tendon differentiation by scleraxis distinguishes force-transmitting tendons from muscle-anchoring tendons
Regulation of tendon differentiation by scleraxis distinguishes force-transmitting tendons from muscle-anchoring tendons
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DOI：
10.1242/dev.001933
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发表时间：
2007-07-15
期刊：
影响因子：
4.6
通讯作者：
Schweitzer, Ronen
中科院分区：
文献类型：
--
作者：
Murchison, Nicholas D.;Price, Brian A.;Schweitzer, Ronen
编码bHLH转录因子的scleraxis（Scx）基因在所有肌腱组织的祖细胞和细胞中表达。为了确定Scx功能，我们产生了突变无效等位基因。Scx（-/-）小鼠是可行的，但表现出严重的肌腱缺陷，这表现在所有爪子和背部肌肉的使用非常有限，完全无法移动尾巴。有趣的是，尽管所有传力肌腱和肌间肌腱的分化都被破坏，但其他类别的肌腱（其功能主要是将肌肉锚在骨骼上）受到的影响较小，并且仍然具有功能，从而使Scx（-/-）突变体能够存活。四肢和尾部的传力肌腱受影响的严重程度各不相同，从祖细胞分化的严重失败导致节段或完整肌腱的损失，到形成小而组织不良的肌腱。肌腱祖细胞在Scx（-/-）胚胎中表现正常，并且在胚胎第13.5天（E）首次检测到肌腱祖细胞凝结失败导致的表型，以产生不同的肌腱。在持续存在Scx（-/-）突变体的肌腱中，我们发现肌腱基质减少且组织化程度较低，细胞水平的组织解体导致肌腱细胞和肌腱内膜细胞混合。Scx（-/-）突变体的表型强调了肌腱组织的多样性，并代表了对肌腱分化重要过程的第一个分子见解。
The scleraxis (Scx) gene, encoding a bHLH transcription factor, is expressed in the progenitors and cells of all tendon tissues. To determine Scx function, we produced a mutant null allele. Scx(-/-) mice were viable, but showed severe tendon defects, which manifested in a drastically limited use of all paws and back muscles and a complete inability to move the tail. Interestingly, although the differentiation of all force-transmitting and intermuscular tendons was disrupted, other categories of tendons, the function of which is mainly to anchor muscles to the skeleton, were less affected and remained functional, enabling the viability of Scx(-/-) mutants. The force- transmitting tendons of the limbs and tail varied in the severity to which they were affected, ranging from dramatic failure of progenitor differentiation resulting in the loss of segments or complete tendons, to the formation of small and poorly organized tendons. Tendon progenitors appeared normal in Scx(-/-) embryos and a phenotype resulting from a failure in the condensation of tendon progenitors to give rise to distinct tendons was first detected at embryonic day (E) 13.5. In the tendons that persisted in Scx(-/-) mutants, we found a reduced and less organized tendon matrix and disorganization at the cellular level that led to intermixing of tenocytes and endotenon cells. The phenotype of Scx(-/-) mutants emphasizes the diversity of tendon tissues and represents the first molecular insight into the important process of tendon differentiation.