From embryogenesis to metamorphosis: The regulation and function of drosophila nuclear receptor superfamily members

From embryogenesis to metamorphosis: The regulation and function of drosophila nuclear receptor superfamily members
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DOI:
10.1016/0092-8674(95)90203-1
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发表时间:
1995-12
期刊:
影响因子:
64.5
通讯作者:
C. Thummel
C. Thummel
中科院分区:
生物学1区
文献类型:
--
作者:
C. Thummel

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核受体超家族的发现和受体功能的详细研究彻底改变了我们对激素作用的理解。对果蝇(Drosophila melanogaster)核受体超家族成员的研究为在发育中的动物背景下定义受体功能提供了理想的模型系统,从而为这些突破做出了贡献。迄今为止,在果蝇中已分离出16个核受体超家族基因,所有基因编码异二聚体和孤儿受体类的成员(Mangelsdorf和Evans,1995年综述[本期Ce//])。一些超家族成员似乎在胚胎阶段特异性地发挥作用,而另一些则在发育的多个阶段需要。值得注意的是,已知的果蝇超家族成员中有一半受到类固醇激素蜕皮激素的调节,似乎有助于与变态相关的复杂发育途径。这篇综述提供了一个简短的调查,我们目前的了解核受体超家族成员如何在果蝇发育过程中的功能,以及他们的活动如何涉及到他们的脊椎动物homology.Drosophila受体,在胚胎发生的功能:进化保护的例子在果蝇胚胎发生在生命周期的第一天,并涉及到最初的分割的动物器官发生。在果蝇核受体超家族成员中,8个似乎在胚胎发育期间执行特定功能,尽管这些基因中的一些也在发育的后期阶段起作用:knirps(kr 10(Nauber et al.,1988)、knirps相关(knrl)(Oro等人,1988; Rothe等人,1989)、胚胎性腺(egon)(Rothe等,1989)、无尾(tll)(Pignoni等,1990)、dHNF 4(Zhong等人,1993)、七喜(svp)(Mlodziket等人,1990)、FTZ-F7(Lavorgnaet al.,1991)和DHR 39(也称为FTZ-F7/3)(Ohno和Petkovich,1992;艾耶尔等人,1993年)。这些基因中的三个,kni、km/和egon,是仅保留编码DNA结合结构域(DBD)的序列的超家族的高度分化的成员(参见Mangelsdorf和Evans,1995中的图1A)。这些蛋白质中不存在配体结合结构域(LBD),表明它们以配体非依赖性方式发挥功能。在这三个基因中,kni已被最详细地研究,并且是正确的腹部分割所需的(Nauber等人,1988年)。W基因也是分割所必需的,以及脑、肠和马氏管的发育
The discovery of the nuclear receptor superfamily and detailed studies of receptor function have revolutionized our understanding of hormone action. Studies of nuclear receptor superfamily members in the fruit fly, Drosophila melanogaster, have contributed to these breakthroughs by providing an ideal model system for defining receptor function in the context of a developing animal. To date, 16 genes of the nuclear receptor superfamily have been isolated in Drosophila, all encoding members of the heterodimeric and orphan classes of receptors(reviewed by Mangelsdorf and Evans, 1995 [this issue of Ce//]). Some superfamily members appear to function specifically during embryonic stages while others are required during multiple stages of development. Remarkably, half of the known Drosophila superfamily members are regulated by the steroid hormone ecdysone and appear to contribute to the complex developmental pathways associated with metamorphosis. This review provides a brief survey of our current understanding of how nuclear receptor superfamily members function during Drosophila development and how their activities relate to those of their vertebrate homologs.Drosophila Receptors That Function during Embryogenesis: Examples of Evolutionary Conservation Embryogenesis in Drosophila occurs during the first day of the life cycle and involves the initial segmentation of the animal followed by organogenesis. Of the Drosophila nuclear receptor superfamily members, eight appear to perform specific functions during embryonic development, although some of these genes also act at later stages of development: knirps (kr10 (Nauber et al., 1988), knirps-related(knrl)(Oro et al., 1988; Rothe et al., 1989), embryonic gonad (egon)(Rothe et al., 1989), tailless (tll)(Pignoni et al., 1990), dHNF4 (Zhong et al. 1993), seven-up (svp)(Mlodziket al., 199O), FTZ-F7 (Lavorgnaet al., 1991), and DHR39 (also called FTZ-F7/3)(Ohno and Petkovich, 1992; Ayer et al., 1993). Three of these genes, kni, km/, and egon, are highly divergent members of the superfamily that have retained only the sequences encoding the DNA-binding domain (DBD)(see Figure 1A in Mangelsdorf and Evans, 1995). The absence of a ligand-binding domain (LBD) in these proteins suggests that they function in a ligand-independent manner. Of these three genes, kni has been studied in the most detail and is required for proper abdominal segmentation(Nauber et al., 1988). The Wgene is also required for segmentation, as well as the development of the brain, gut, and Malpighian tubules