The nuclear orphan receptor COUP-TFII is required for limb and skeletal muscle development
The nuclear orphan receptor COUP-TFII is required for limb and skeletal muscle development
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DOI：
10.1128/mcb.24.24.10835-10843.2004
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发表时间：
2004-12-01
影响因子：
5.3
通讯作者：
Tsai, SY
中科院分区：
文献类型：
--
作者：
Lee, CT;Li, LP;Tsai, SY
核孤儿受体COUP-TFII在胚胎发育过程中广泛表达于多种组织和器官，提示COUP-TFII参与胚胎发生的多个方面。由于COUP-TFII基因敲除小鼠的早期胚胎致死性，COUP-TFII在肢体发育中的作用尚未确定。COUP-TFII在肢芽形成前的早期胚胎的侧板中胚层中表达。此外，COUP-TFII在肢体的体节和骨骼肌前体细胞中也有表达。因此，为了研究COUP-TFII在肢体和骨骼肌发育中的潜在作用，我们通过两种方法绕过了COUP-TFII突变体的早期胚胎致死性。首先，胚胎嵌合体分析揭示了Coup-TFII在肢芽生长中的必备作用，因为突变细胞无法促进远端生长的肢体间充质。其次，我们使用了一种有条件的敲除方法来消除政变-TFII，特别是在四肢。在四肢中失去Coup-TFII会导致骨骼肌发育不良，以及四肢变短。综上所述，我们的结果表明COUP-TFII在肢芽生长中起早期作用，而不是肢芽起始。此外，COUP-TFII对于发育中四肢的骨骼肌肉系统的适当发育也是必需的。
The nuclear orphan receptor COUP-TFII is widely expressed in multiple tissues and organs throughout embryonic development, suggesting that COUP-TFII is involved in multiple aspects of embryogenesis. Because of the early embryonic lethality of COUP-TFII knockout mice, the role of COUP-TFII during limb development has not been determined. COUP-TFII is expressed in lateral plate mesoderm of the early embryo prior to limb bud formation. In addition, COUP-TFII is also expressed in the somites and skeletal muscle precursors of the limbs. Therefore, in order to study the potential role of COUP-TFII in limb and skeletal muscle development, we bypassed the early embryonic lethality of the COUP-TFII mutant by using two methods. First, embryonic chimera analysis has revealed an obligatory role for COUP-TFII in limb bud outgrowth since mutant cells are unable to contribute to the distally growing limb mesenchyme. Second, we used a conditional-knockout approach to ablate COUP-TFII specifically in the limbs. Loss of COUP-TFII in the limbs leads to hypoplastic skeletal muscle development, as well as shorter limbs. Taken together, our results demonstrate that COUP-TFII plays an early role in limb bud outgrowth but not limb bud initiation. Also, COUP-TFII is required for appropriate development of the skeletal musculature of developing limbs.