The zinc finger homeodomain-2 gene of Drosophila controls Notch targets and regulates apoptosis in the tarsal segments
The zinc finger homeodomain-2 gene of Drosophila controls Notch targets and regulates apoptosis in the tarsal segments
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DOI：
10.1016/j.ydbio.2013.10.011
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发表时间：
2014-01-15
影响因子：
2.7
通讯作者：
Sanchez-Herrero, Ernesto
中科院分区：
文献类型：
--
作者：
Guarner, Ana;Manjon, Cristina;Sanchez-Herrero, Ernesto
果蝇腿的发育是研究图案形成、细胞死亡和分裂过程的良好模型。这样的过程需要不同基因和信号通路的协调活动，逐步将腿部区域细分为更小的区域。腿发育所需的主要途径之一是Notch通路，它是确定腿的近端-远端轴和形成分隔不同腿段的关节所必需的。协调这类事件所需的机制在很大程度上是未知的。我们在这里描述了锌指同源域-2(zfh-2)基因在形成腿关节的细胞中高度表达，并需要在远端腿中建立正确的大小和模式。ZFH-2早期需要建立正确的近远轴，但在三龄后期也需要ZFH-2形成第四节和第五节之间的关节。ZFH-2的表达需要Notch的活性，而ZFH-2又是激活Notch靶点所必需的，如Split增强子和大脑。ZFH-2受果蝇激活蛋白2基因控制，调控无眼睑的晚期表达。在缺乏ZFH-2的情况下，许多细胞异位表达促凋亡基因头部退化缺陷，激活caspase-3，并呈吖啶橙阳性，表明它们发生了凋亡。我们的结果证明了ZFH-2在腿部发育过程中控制细胞死亡和Notch信号转导中的关键作用。(C)2013 Elsevier Inc.保留所有权利。
The development of the Drosophila leg is a good model to study processes of pattern formation, cell death and segmentation. Such processes require the coordinate activity of different genes and signaling pathways that progressively subdivide the leg territory into smaller domains. One of the main pathways needed for leg development is the Notch pathway, required for determining the proximo-distal axis of the leg and for the formation of the joints that separate different leg segments. The mechanisms required to coordinate such events are largely unknown. We describe here that the zinc finger homeodomain-2 (zfh-2) gene is highly expressed in cells that will form the leg joints and needed to establish a correct size and pattern in the distal leg. There is an early requirement of zfh-2 to establish the correct proximo-distal axis, but zfh-2 is also needed at late third instar to form the joint between the fourth and fifth tarsal segments. The expression of zfh-2 requires Notch activity but zfh-2 is necessary, in turn, to activate Notch targets such as Enhancer of split and big brain. zfh-2 is controlled by the Drosophila activator protein 2 gene and regulates the late expression of tarsal-less. In the absence of zfh-2 many cells ectopically express the pro-apoptotic gene head involution defective, activate caspase-3 and are positive for acridine orange, indicating they undergo apoptosis. Our results demonstrate the key role of zfh-2 in the control of cell death and Notch signaling during leg development. (C) 2013 Elsevier Inc. All rights reserved.