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果蝇上颌触须发育过程中 Wnt 基因的调控和功能。

Wnt gene regulation and function during maxillary palp development in Drosophila melanogaster.

机构信息

Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, OX3 0BP, United Kingdom; Division of Signalling and Functional Genomics, German Cancer Research Centre (DKFZ), Department of Cell and Molecular Biology, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.

Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, OX3 0BP, United Kingdom.

出版信息

Dev Biol. 2020 Jun 1;462(1):66-73. doi: 10.1016/j.ydbio.2020.03.012. Epub 2020 Mar 27.

Abstract

Wnt genes encode secreted ligands that play many important roles in the development of metazoans. There are thirteen known Wnt gene subfamilies and seven of these are represented in Drosophila melanogaster. While wingless (wg) is the best understood and most widely studied Wnt gene in Drosophila, the functions of many of the other Drosophila Wnt genes are less well understood. For example, relatively little is known about Wnt6, which is an ancient paralog of wg and they form a conserved Wnt cluster together with Wnt9 (Dwnt4) and Wnt10. Wg and Wnt6 encode similar proteins and exhibit overlapping expression in several tissues during development. Both wg and Wnt6 were previously shown to regulate the development of maxillary palps, important olfactory organs in flies, but it remained unclear how these two ligands may combine to carry out specific functions and how this is regulated. Here, we have further analysed Wnt6 function in the context of maxillary palp development. Surprisingly, we found that Wnt6 does not appear to be necessary for development of maxillary palps. While a deletion of the 5' region of Wnt6 results in very small maxillary palps, we show that this effect is more likely to be a consequence of removing cis-regulatory elements that may regulate wg expression in this tissue rather than through the loss of Wnt6 function. Although, we cannot completely exclude the possibility that Wnt6 may subtly regulate maxillary palp development in combination with wg, our analysis of Wnt6 loss of function mutants suggests this ligand plays a more general role in regulating growth during development. Taken together our results provide new insights into maxillary palp formation and Wnt6 functions in Drosophila, and further evidence for a complex cis-regulatory landscape in the Wnt9-wg-Wnt6-Wnt10 cluster, which may help explain its evolutionary conservation.

摘要

Wnt 基因编码的分泌配体在后生动物的发育中发挥着许多重要作用。已知有 13 个 Wnt 基因亚家族,其中 7 个在果蝇中得到了体现。虽然无翅(wg)是果蝇中研究最为广泛和深入的 Wnt 基因,但其他许多果蝇 Wnt 基因的功能却知之甚少。例如,关于 Wnt6,它是 wg 的古老同源基因,与 Wnt9(Dwnt4)和 Wnt10 一起形成一个保守的 Wnt 簇,人们对其了解相对较少。Wg 和 Wnt6 编码相似的蛋白质,并在发育过程中在几个组织中表现出重叠表达。以前已经证明 wg 和 Wnt6 都可以调节触角的发育,触角是果蝇中重要的嗅觉器官,但仍不清楚这两种配体如何结合以执行特定功能以及如何进行调节。在这里,我们在触角发育的背景下进一步分析了 Wnt6 的功能。令人惊讶的是,我们发现 Wnt6 似乎不是触角发育所必需的。尽管 Wnt6 的 5' 区域缺失会导致触角非常小,但我们表明,这种效应更可能是由于去除了可能调节该组织中 wg 表达的顺式调控元件,而不是由于 Wnt6 功能的丧失。尽管我们不能完全排除 Wnt6 可能与 wg 一起微妙地调节触角发育的可能性,但我们对 Wnt6 功能丧失突变体的分析表明,该配体在调节发育过程中的生长中起着更普遍的作用。总之,我们的研究结果为果蝇触角形成和 Wnt6 功能提供了新的见解,并进一步证明了 Wnt9-wg-Wnt6-Wnt10 簇中存在复杂的顺式调控景观,这可能有助于解释其进化保守性。

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