Investigating the specification and evolution of organ size in Drosophila

研究果蝇器官大小的规格和演变

• 批准号: BB/X006689/1
• 负责人: Alistair McGregor
• 金额: $ 63.79万
• 依托单位: Durham University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX006689%2F1
• 关键词: Investigating; specification; evolution; organ; size

The organs of animals have to be the correct size so that they can function properly and yet during the course of evolution organ size can change between species. We have growing knowledge of how organ growth is controlled but a poor understanding of how final size is specified. Furthermore, in some case we understand how changes in cell number, size or shape result in evolutionary changes in organ size between species but the causative genes are not known or vice versa. We have found that the gene tartan (trn) helps to specify the size of Drosophila claspers, male genital organs of these flies with important roles in copulation, but that differences in trn expression have also evolved to change clasper size between D. mauritiana and D. simulans. This represents an excellent opportunity to understand the genetic and cellular bases of organ size on one hand and how these mechanisms evolve to result in differences in organ size on the other.Trn protein is expressed in cell membranes. On the outside of cells, Trn marks their identity and signals this information to neighbouring cells to respond. On the inside of cells, Trn interacts with other proteins to regulate cell identity and position, and transmits information from its binding to other cells. Through these molecular functions, Trn helps to form boundaries within and between developing organs, including body segments, eyes, wings, and legs as well as genitalia, to ensure cells are correctly located based on their identity. Our preliminary data suggest that Trn and another protein Tenascin-major (Ten-m) form a boundary that helps to determine clasper size. We have also found that clasper size is regulated by the transcription factor C15 potentially restricting Trn expression within the clasper and by Cpr66D in the extra-cellular matrix. However, we don't know how trn gene expression and Trn protein interactions with other proteins combine to control how many cells, of what size and in what location make claspers of the correct size nor how these mechanisms evolve to change cells and therefore organ size between species. Therefore, we will study and quantify cell boundaries, number, size, division and movement during clasper formation and how this is influenced by Trn in D. melanogaster. We will also explore how this is regulated through potential interactions between Trn, hairy, ten-M, C15 and Cpr66D, and identify new proteins that directly interact with Trn to better understand its function. These experiments will provide new knowledge about how clasper size is regulated by trn and other genes, inform how Trn functions in developing Drosophila genitalia as well as other tissues and other animals, and further our understanding of organ size specification more generally. Studying differences in traits between species can often provide new insights into how these traits develop as well the basis for their evolution. Therefore, to complement our experiments investigating clasper development in D. melanogaster, we will study how natural variation in Trn expression changes cells to cause evolutionary differences in clasper size between D. mauritiana and D. simulans. Furthermore, since our developmental candidate genes hairy, ten-M, C15 and Cpr66D all map to regions of the genome that underlie differences in clasper size between D. mauritiana and D. simulans, we will also directly test if and how they contribute to clasper size evolution to more fully understand the genetic and cellular bases of this organ size difference. Taken together, we anticipate that our synthesis of development and evolution will provide important new insights into organ size regulation and transform understanding of how the molecular mechanisms that control organ size evolve to change cells to build organs of different sizes between species.

动物的器官必须有正确的大小，这样它们才能正常运作，但在进化过程中，器官的大小可能会因物种而异。我们对器官生长是如何控制的有了越来越多的了解，但对最终大小是如何指定的了解很少。此外，在某些情况下，我们了解细胞数量、大小或形状的变化如何导致物种之间器官大小的进化变化，但致病基因未知，反之亦然。我们已经发现，tartan(Trn)基因有助于指定果蝇扣子的大小，这些果蝇的雄性生殖器官在交配中起着重要作用，但trn表达的差异也进化到改变了毛果果蝇和拟果蝇之间的扣子大小。这是一个很好的机会，一方面可以了解器官大小的遗传和细胞基础，另一方面这些机制是如何进化到导致器官大小不同的。Trn蛋白在细胞膜中表达。在细胞的外部，Trn标记它们的身份，并将该信息发送给相邻细胞以做出反应。在细胞内部，Trn与其他蛋白质相互作用，调节细胞的身份和位置，并将其结合的信息传递给其他细胞。通过这些分子功能，Trn有助于在发育中的器官内部和之间形成边界，包括身体部分、眼睛、翅膀和腿以及生殖器，以确保细胞根据其身份被正确定位。我们的初步数据表明，Trn和另一种蛋白质Tenascin-Major(Ten-m)形成了一条边界，有助于确定夹子的大小。我们还发现，夹子的大小受转录因子C15的调节，C15可能限制Trn在夹子内的表达，而Cpr66D则限制细胞外基质的表达。然而，我们不知道trn基因的表达和trn蛋白与其他蛋白质的相互作用如何结合来控制多少细胞、多大小和在什么位置产生正确大小的扣子，也不知道这些机制如何进化来改变细胞，从而改变物种之间的器官大小。因此，我们将研究和量化细胞边界、数量、大小、分裂和运动在扣环形成过程中，以及Trn是如何影响黑腹果蝇这一过程的。我们还将探索如何通过Trn、Haily、Ten-M、C15和Cpr66D之间的潜在相互作用来调节这一过程，并寻找与Trn直接相互作用的新蛋白，以更好地了解其功能。这些实验将提供关于trn和其他基因如何调节夹子大小的新知识，了解trn在发育中的果蝇生殖器以及其他组织和其他动物中的作用，并进一步加深我们对器官大小指定的更广泛的理解。研究物种之间的特征差异通常可以为这些特征是如何发展的提供新的见解，也是它们进化的基础。因此，为了补充我们研究黑腹盘藻扣环发育的实验，我们将研究Trn表达的自然变异如何改变细胞，从而导致毛盘盘藻和拟黑腹盘藻在扣环大小上的进化差异。此外，由于我们的发育候选基因Haily、Ten-M、C15和Cpr66D都定位于毛滴虫和拟毛滴虫在卡环大小上存在差异的基因组区域，我们还将直接测试它们是否以及如何对卡环大小的进化做出贡献，以更全面地了解这种器官大小差异的遗传和细胞基础。综上所述，我们预计我们对发育和进化的综合将为器官大小调控提供重要的新见解，并改变对控制器官大小的分子机制如何进化到改变细胞以建立不同物种之间不同大小的器官的理解。

项目成果

Sox21b underlies the rapid diversification of a novel male genital structure between Drosophila species

• DOI: 10.1016/j.cub.2024.01.022
• 发表时间: 2024-03-11
• 期刊: CURRENT BIOLOGY
• 影响因子: 9.2
• 作者: Ridgway，Amber M.;Hood，Emily J.;Mcgregor，Alistair P.
• 通讯作者: Mcgregor，Alistair P.