Distinct functions of homothorax in leg development in Drosophila

Distinct functions of homothorax in leg development in Drosophila
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DOI:
10.1016/s0925-4773(02)00295-2
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发表时间:
2002-11-01
影响因子:
2.6
通讯作者:
Morata, G
Morata, G
中科院分区:
生物学4区
文献类型:
--
作者:
Azpiazu, N;Morata, G

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果蝇的腿被细分为两个相互对抗的近端和远端区域。近端结构域由同源异型盒基因同源胸腔和外牙突起的活性定义,远端结构域由DPP/Wg靶标Distal-less(Dll)和Dachshund(DAC)定义。已知hth/exd功能阻止DPP和Wg反应基因的活性,并且在近端区域缺乏EXD活性的细胞分化与腿部更远端区域相对应的图案元件。我们报道了hTH/EXD拮抗DPP途径的新结果。在腿部远端表达hth的细胞中,存在DPP途径的衰弱,这反映在Mad磷酸化水平的降低和受体厚静脉水平的增加。异位hth在小腿远端的表达导致JNK介导的细胞凋亡,生长减慢和模式异常。它还导致附件的普遍近似化,这可以用干扰DPP和WG通路来解释。我们还报道了hth/exd对DPP和Wg靶标末端的抑制不是在转录水平上实现的,而是阻止了DLL靶基因的激活。我们认为,hth/exd功能通过限制DPP和Wg通路的影响以及激活近端基因如teashirt(Tsh)和aristess(Al)来促进近端细胞的正常识别。(C)2002爱思唯尔科学有限公司。保留所有权利。
The Drosophila leg is subdivided into two mutually antagonistic proximal and distal domains. The proximal domain is defined by the activity of the homeobox genes homothorax and extradenticle and the distal one by the Dpp/Wg targets Distal-less (Dll) and dachshund (dac). It is known that hth/exd function prevents the activity of Dpp and Wg response genes and that cells deficient for exd activity in the proximal domain differentiate pattern elements corresponding to more distal leg regions. We report new results on the role of hth/exd antagonising the Dpp pathway. In cells expressing hth in the distal leg, there is a debilitation of the Dpp pathway which is reflected in lower levels of Mad phosphorylation and in increased levels of the receptor thick veins. Ectopic hth expression in the distal leg results in, JNK-mediated apoptosis, decreased growth and pattern abnormalities. It also causes a general proximalisation of the appendage, which can be explained by interference with the Dpp and Wg pathways. We also report that the repression by hth/exd of the Dpp and Wg target Distal-less is not achieved at the level of transcription but preventing the activation of Dll target genes. We propose that hth/exd function contributes to the normal identity of proximal cells both by limiting the influence of the Dpp and Wg pathways and by activating proximal genes like teashirt (tsh) and aristaless (al). (C) 2002 Elsevier Science Ltd. All rights reserved.