Drosophila T-box transcription factor Optomotor-blind prevents pathological folding and local overgrowth in wing epithelium through confining Hh signal.
Drosophila T-box transcription factor Optomotor-blind prevents pathological folding and local overgrowth in wing epithelium through confining Hh signal.
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DOI：
10.1016/j.ydbio.2007.05.007
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发表时间：
2007-08
影响因子：
2.7
通讯作者：
Makoto Umemori;Masahiko Takemura;Kousuke Maeda;Keisuke Ohba;T. Adachi-Yamada
中科院分区：
文献类型：
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作者：
Makoto Umemori;Masahiko Takemura;Kousuke Maeda;Keisuke Ohba;T. Adachi-Yamada
形态发生素信号传导的异常直接导致不适当的细胞分化，进而引起形态发生异常和肿瘤发生等各种病理表型。然而，连接形态发生素信号传导和高阶表型的机制尚未完全阐明。在这里，我们重点关注果蝇 T-box 基因 optomotor-blind (omb)，它是远程形态发生素 Decapentaplegic (Dpp) 的转录靶标。 omb 功能的遗传分析表明，Dpp 与其上游调节因子 Hedgehog (Hh)（一种短程形态发生素）之间存在负反馈环，其中 omb 起着至关重要的作用。因此，omb 功能障碍会引起 Hh 信号过度激活，从而导致翼柱状上皮异位折叠和局部过度生长，而这两者都不是 Dpp 反应减少的直接结果。在局部过度生长的情况下，在编码 Dpp 受体的粗静脉 (tkv) 突变体中从未见过，这表明 Dpp 信号通路分为两个拮抗分支，其中之一包含 Omb。因此，两种形态发生素之间的反馈缺陷解释了这两种表型，而形态发生素靶标之间平衡的破坏进一步解释了局部过度生长。这些是当单个信号因子 Omb 无法发挥作用时产生次级表型的机制。
Aberration of morphogen signaling leads directly to inappropriate cell differentiation and secondarily causes various pathological phenotypes such as abnormal morphogenesis and tumorigenesis. However, mechanisms for linking morphogen signaling and the higher order phenotypes have not been fully elucidated. Here we focus on the Drosophila T-box gene optomotor-blind (omb), a transcriptional target of a long-range morphogen Decapentaplegic (Dpp). Genetic analyses of omb function revealed that a negative feedback loop, where omb plays a crucial role, exists between Dpp and its upstream regulator Hedgehog (Hh), a short-range morphogen. Consequently, dysfunction of omb elicits hyperactivation of Hh signaling that causes an ectopic folding and local overgrowth in the wing columnar epithelium, neither of which are the direct results of reduced Dpp response. In the case of the local overgrowth, it was never seen in mutants for thick veins (tkv) encoding a Dpp receptor, suggesting that the Dpp signaling pathway is divided into two antagonistic branches, one of which contains Omb. Thus defect in feedback between the two morphogens explains both phenotypes, and disruption of a balance between the morphogen targets further accounts for the local overgrowth. These are the mechanisms for generating secondary phenotypes when a single signaling factor Omb fails to function.