The ETS domain transcriptional repressor Anterior open inhibits MAP kinase and Wingless signaling to couple tracheal cell fate with branch identity
The ETS domain transcriptional repressor Anterior open inhibits MAP kinase and Wingless signaling to couple tracheal cell fate with branch identity
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DOI：
10.1242/dev.087874
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发表时间：
2013-03-01
期刊：
影响因子：
4.6
通讯作者：
Luschnig, Stefan
中科院分区：
文献类型：
--
作者：
Caviglia, Sara;Luschnig, Stefan
果蝇气管系统中萌芽分支顶端的细胞产生两种形态上不同类型的无缝管。末端细胞(TC)形成分枝的管腔延伸，介导靶组织的气体交换，而融合细胞(FCS)在相邻的气管异构体之间形成环状连接。每个气管分支包含一组特定的TC、FCS或两者，但以分支特有的方式在两种尖端细胞类型之间进行选择的机制尚不清楚。在这里，我们表明，Ets结构域转录抑制因子前开放(AOP)对于气管细胞的定向迁移是必不可少的，但在气管尖端细胞命运的指定中起着关键作用。虽然AOP在全球范围内抑制TC和FC规范，但MAPK信号通过触发TIP细胞中AOP的降解来克服这种抑制。AOP功能的丧失导致FC和TC的过度指定，表明在没有AOP介导的抑制作用的情况下，所有的气管细胞都有能力采用特殊的命运。我们证明，AOP通过抑制MAPK和Wingless信号，分别诱导TC和FC命运，发挥双重作用。此外，在两种无缝管类型之间的分支特异性选择取决于气管分支识别基因Spalt main，该基因足以抑制TC规范。因此，一个单一的抑制子，AOP，整合了两个不同的信号，将尖端细胞命运选择与分支身份结合起来。从分支向吻合的尖端细胞类型的转变可能是随着主管的获得而演变的，主管连接不同的气管原基以产生管状网络。
Cells at the tips of budding branches in the Drosophila tracheal system generate two morphologically different types of seamless tubes. Terminal cells (TCs) form branched lumenized extensions that mediate gas exchange at target tissues, whereas fusion cells (FCs) form ring-like connections between adjacent tracheal metameres. Each tracheal branch contains a specific set of TCs, FCs, or both, but the mechanisms that select between the two tip cell types in a branch-specific fashion are not clear. Here, we show that the ETS domain transcriptional repressor anterior open (aop) is dispensable for directed tracheal cell migration, but plays a key role in tracheal tip cell fate specification. Whereas aop globally inhibits TC and FC specification, MAPK signaling overcomes this inhibition by triggering degradation of Aop in tip cells. Loss of aop function causes excessive FC and TC specification, indicating that without Aop-mediated inhibition, all tracheal cells are competent to adopt a specialized fate. We demonstrate that Aop plays a dual role by inhibiting both MAPK and Wingless signaling, which induce TC and FC fate, respectively. In addition, the branch-specific choice between the two seamless tube types depends on the tracheal branch identity gene spalt major, which is sufficient to inhibit TC specification. Thus, a single repressor, Aop, integrates two different signals to couple tip cell fate selection with branch identity. The switch from a branching towards an anastomosing tip cell type may have evolved with the acquisition of a main tube that connects separate tracheal primordia to generate a tubular network.