The homeodomain protein ladybird late regulates synthesis of milk proteins during pregnancy in the tsetse fly (Glossina morsitans).
The homeodomain protein ladybird late regulates synthesis of milk proteins during pregnancy in the tsetse fly (Glossina morsitans).
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DOI：
10.1371/journal.pntd.0002645
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发表时间：
2014-04
影响因子：
3.8
通讯作者：
Aksoy S
中科院分区：
文献类型：
--
作者：
Attardo GM;Benoit JB;Michalkova V;Patrick KR;Krause TB;Aksoy S
组织和发育特异性基因表达模式的调节是多细胞生物体器官功能特化的基础。在胎生采采蝇（Glossina）中，雌性附腺专门以乳样分泌物的形式产生营养物质，以支持子宫内幼虫的生长。多个乳蛋白基因在雌性附腺中特异表达，并与幼虫发育密切相关。乳蛋白合成的中断剥夺了发育中的幼虫的营养物质，并导致幼虫发育延长和/或流产。造成这种破坏的能力可以用作采采蝇控制策略。在这里，我们确定和描绘的主要乳蛋白基因（乳腺蛋白1：mgp 1）的调控序列，利用在采采蝇，果蝇转基因，转录组学和硅序列分析的分子技术的组合。该启动子的功能在采采蝇和果蝇之间是保守的。在转基因果蝇中，mgp 1启动子以与Glossina的组织和阶段特异性方式正交的方式指导报告基因的表达。最小所需的MGP 1的调控区，和其他Glossina乳蛋白的调控区的分析确定推定的同源结构域蛋白结合位点作为唯一的共同特征。Glossina同源结构域蛋白的注释和表达分析鉴定瓢虫晚期（lbl）为附属腺/脂肪体特异性的，并且在哺乳/非哺乳果蝇之间差异表达。在采采蝇中敲除lbl导致多个乳蛋白基因的转录丰度显著降低，并导致繁殖力显著下降。Lbl在成年生殖生理学中的作用以前是未知的。这些结果表明，Lbl是一个保守的生殖调控系统的一部分，可能有超越采采蝇的其他媒介昆虫，如蚊子的影响。该系统对采采蝇繁殖力至关重要，并为生殖抑制剂的开发提供了潜在的靶点。雌性采采蝇（双翅目：舌蝇科）窝藏和生育活的年轻人。为了做到这一点，它们用乳汁分泌物滋养子宫内的幼虫。这项工作的重点是了解采采蝇乳蛋白的调节，这是繁殖力所必需的，并在怀孕的女性在时间和空间上的特定方式表达。我们确定了最小的上游调控DNA序列的主要牛奶蛋白基因mgp 1，赋予组织特异性表达的女性附属腺的繁殖活跃的苍蝇。该调控序列在转基因果蝇（Drosophila melanogaster）中具有类似的功能，并驱动报告基因产物在成年雌性附腺中的表达。这种调控序列与其他特征的牛奶蛋白序列的比较表明，保守的同源结构域转录因子可能是负责调节这些基因。Glossina同源结构域蛋白的分析确定了一个附属腺/脂肪体特异性因子，瓢虫晚（lbl），这似乎调节多种乳蛋白的表达。lbl水平的降低会干扰乳蛋白基因表达，从而降低Glossina的繁殖力。这些结果表明，乳蛋白Glossina的调节由一个保守的调节系统介导的同源结构域转录因子lbl的一部分。该系统的组成部分可以为采采蝇生殖抑制剂的开发提供靶点。
Regulation of tissue and development specific gene expression patterns underlies the functional specialization of organs in multi-cellular organisms. In the viviparous tsetse fly (Glossina), the female accessory gland is specialized to generate nutrients in the form of a milk-like secretion to support growth of intrauterine larva. Multiple milk protein genes are expressed specifically in the female accessory gland and are tightly linked with larval development. Disruption of milk protein synthesis deprives developing larvae of nutrients and results in extended larval development and/or in abortion. The ability to cause such a disruption could be utilized as a tsetse control strategy. Here we identify and delineate the regulatory sequence of a major milk protein gene (milk gland protein 1:mgp1) by utilizing a combination of molecular techniques in tsetse, Drosophila transgenics, transcriptomics and in silico sequence analyses. The function of this promoter is conserved between tsetse and Drosophila. In transgenic Drosophila the mgp1 promoter directs reporter gene expression in a tissue and stage specific manner orthologous to that of Glossina. Analysis of the minimal required regulatory region of mgp1, and the regulatory regions of other Glossina milk proteins identified putative homeodomain protein binding sites as the sole common feature. Annotation and expression analysis of Glossina homeodomain proteins identified ladybird late (lbl) as being accessory gland/fat body specific and differentially expressed between lactating/non-lactating flies. Knockdown of lbl in tsetse resulted in a significant reduction in transcript abundance of multiple milk protein genes and in a significant loss of fecundity. The role of Lbl in adult reproductive physiology is previously unknown. These results suggest that Lbl is part of a conserved reproductive regulatory system that could have implications beyond tsetse to other vector insects such as mosquitoes. This system is critical for tsetse fecundity and provides a potential target for development of a reproductive inhibitor. Female tsetse flies (Diptera: Glossina) harbor and give birth to live young. To do this, they nourish their intrauterine larvae with milk secretions. This work focuses upon understanding the regulation of tsetse milk proteins, which are essential for fecundity and are expressed in a temporally and spatially specific manner by pregnant females. We identified the minimal upstream regulatory DNA sequence of the major milk protein gene mgp1, which confers tissue specific expression in the female accessory glands of reproductively active flies. This regulatory sequence functions similarly in transgenic fruit flies (Drosophila melanogaster) and drives expression of reporter gene products in the adult female accessory gland. Comparison of this regulatory sequence with sequences from other characterized milk proteins indicates that conserved homeodomain transcription factors may be responsible for regulating these genes. Analysis of Glossina homeodomain proteins identified an accessory gland/fat body specific factor, Ladybird late (lbl), which appears to regulate the expression of multiple milk proteins. Reduction of lbl levels interferes with milk protein gene expression, which in turn reduces Glossina fecundity. These results suggest that milk proteins in Glossina are regulated by a conserved regulatory system mediated in part by the homeodomain transcription factor lbl. Components of this system could provide a target for development of a tsetse reproductive inhibitor.
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影响因子：
4.4
作者：
Attardo GM;Ribeiro JM;Wu Y;Berriman M;Aksoy S
通讯作者：
Aksoy S
影响因子：
3.3
作者：
Bateman, Jack R.;Lee, Anne M.;Wu, C. -ting
通讯作者：
Wu, C. -ting
影响因子：
1.9
作者：
LANGLEY, PA;PIMLEY, RW
通讯作者：
PIMLEY, RW
影响因子：
5.8
作者：
Cartharius, K;Frech, K;Werner, T
通讯作者：
Werner, T
影响因子：
2.2
作者：
Attardo, Geoffrey M.;Lohs, Claudia;Heddi, Abdelaziz;Alam, Uzma H.;Yildirim, Suleyman;Aksoy, Serap
通讯作者：
Aksoy, Serap