Tbx5 is dispensable for forelimb outgrowth
Tbx5 is dispensable for forelimb outgrowth
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DOI：
10.1242/dev.02622
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发表时间：
2007-01-01
期刊：
影响因子：
4.6
通讯作者：
Logan, Malcolm P. O.
中科院分区：
文献类型：
--
作者：
Hasson, Peleg;Del Buono, Joanne;Logan, Malcolm P. O.
Tbx5 对于前肢的启动至关重要，在小鼠中缺失该基因会导致前肢形成失败。 Tbx5 显性失活形式的错误表达会导致肢体截断，这表明 Tbx5 也是前肢生长所必需的。在这里，我们表明 Tbx5 在软骨、肌腱和肌肉祖细胞的整个肢体间质中表达。使用他莫昔芬诱导的 Cre 转基因系，我们绘制了肢体发育所需 Tbx5 的时间范围。我们表明，肢体起始后删除 Tbx5 不会损害肢体的生长。此外，我们区分了肢体发育的两个不同阶段：Tbx5 依赖性肢体起始阶段，随后是 Tbx5 独立肢体生长阶段。在人类中，T 盒转录因子 TBX5 的突变与显性疾病 Holt-Oram 综合征 (HOS) 相关，该综合征的特征是前肢和心脏畸形。我们的结果表明，早期肢体发育过程中对 Tbx5 的需求时间较短，并表明 HOS 中发现的缺陷是由于在这段狭窄的时间窗口内 TBX5 功能被破坏而产生的。
Tbx5 is essential for initiation of the forelimb, and its deletion in mice results in the failure of forelimb formation. Misexpression of dominant-negative forms of Tbx5 results in limb truncations, suggesting Tbx5 is also required for forelimb outgrowth. Here we show that Tbx5 is expressed throughout the limb mesenchyme in progenitors of cartilage, tendon and muscle. Using a tamoxifen-inducible Cre transgenic line, we map the time frame during which Tbx5 is required for limb development. We show that deletion of Tbx5 subsequent to limb initiation does not impair limb outgrowth. Furthermore, we distinguish two distinct phases of limb development: a Tbx5-dependent limb initiation phase, followed by a Tbx5-independent limb outgrowth phase. In humans, mutations in the T-box transcription factor TBX5 are associated with the dominant disorder Holt-Oram syndrome (HOS), which is characterised by malformations in the forelimb and heart. Our results demonstrate a short temporal requirement for Tbx5 during early limb development, and suggest that the defects found in HOS arise as a result of disrupted TBX5 function during this narrow time window.