Role of T-box gene tbx-2 for anterior foregut muscle development in C. elegans.
Role of T-box gene tbx-2 for anterior foregut muscle development in C. elegans.
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DOI：
10.1016/j.ydbio.2006.08.023
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发表时间：
2007-02
影响因子：
2.7
通讯作者：
Pliny A. Smith;S. Mango
中科院分区：
文献类型：
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作者：
Pliny A. Smith;S. Mango
在器官发生过程中，多能前体细胞获得明确的身份，例如肌肉或神经。从幼稚前体向分化状态的转变的特征是由调控转录因子决定的基因表达的连续波。一个关键问题是转录回路如何决定伴随发育能力、细胞命运规范和分化的一系列事件。为了解决这个问题，我们研究了秀丽隐杆线虫前肠（咽）内的前部肌肉是如何形成的。我们发现 T-box 转录因子 tbx-2 对于 ABa 卵裂球形成前咽肌至关重要。在缺乏 tbx-2 功能的情况下，ABa 衍生细胞正常启动发育：它们接收 glp-1/Notch 信号传导信号，激活 T 盒基因 TBX-38 并表达器官选择基因 PHA-4/FoxA。然而，这些细胞随后阻碍发育，消灭 PHA-4 并且无法激活 PHA-4 靶基因。 tbx-2突变细胞不会发生细胞凋亡，并且没有证据表明采用其他命运。 TBX-2 在 ABa 后代中表达，依赖于 pha-4 的激活和 glp-1/Notch 信号传导成分的抑制。我们的分析表明，ABa 衍生的前体细胞决定咽肌命运需要 tbx-2 和 pha-4 之间的正反馈回路。
During organogenesis, pluripotent precursor cells acquire a defined identity such as muscle or nerve. The transition from naïve precursor towards the differentiated state is characterized by sequential waves of gene expression that are determined by regulatory transcription factors. A key question is how transcriptional circuitry dictates the succession of events that accompanies developmental competence, cell fate specification and differentiation. To address this question, we have examined how anterior muscles are established within the Caenorhabditis elegans foregut (pharynx). We find that the T-box transcription factor tbx-2 is essential to form anterior pharyngeal muscles from the ABa blastomere. In the absence of tbx-2 function, ABa-derived cells initiate development normally: they receive glp-1/Notch signaling cues, activate the T-box gene TBX-38 and express the organ selector gene PHA-4/FoxA. However, these cells subsequently arrest development, extinguish PHA-4 and fail to activate PHA-4 target genes. tbx-2 mutant cells do not undergo apoptosis and there is no evidence for adoption of an alternative fate. TBX-2 is expressed in ABa descendants and depends on activation by pha-4 and repression by components of glp-1/Notch signaling. Our analysis suggests that a positive feedback loop between tbx-2 and pha-4 is required for ABa-derived precursors to commit to pharyngeal muscle fate.