Investigating the specification and evolution of organ size in Drosophila

动物的器官必须有正确的大小，这样它们才能正常工作，但在进化过程中，器官的大小可以在物种之间发生变化。我们对器官生长是如何控制的了解越来越多，但对最终大小是如何确定的了解很少。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，但致病基因尚不清楚，反之亦然。我们已经发现，基因tartan（trn）有助于指定果蝇的抱器，这些苍蝇的雄性生殖器官的大小在交配中发挥重要作用，但在trn表达的差异也演变为改变果蝇之间的抱器大小。mauritiana和D. simulans。这是一个很好的机会，一方面了解器官大小的遗传和细胞基础，以及这些机制如何演变导致器官大小的差异。Trn蛋白在细胞膜中表达。在细胞的外部，Trn标记它们的身份，并将此信息发送给相邻细胞以做出响应。在细胞内部，Trn与其他蛋白质相互作用以调节细胞身份和位置，并将其结合的信息传递给其他细胞。通过这些分子功能，Trn有助于在发育器官（包括身体部位、眼睛、翅膀和腿以及生殖器）内部和之间形成边界，以确保细胞根据其身份正确定位。我们的初步数据表明，Trn和另一种蛋白质Tenascin-major（Ten-m）形成了一个边界，有助于确定clasper大小。我们还发现，clasper大小调节的转录因子C15可能限制Trn表达内的clasper和Cpr 66 D在细胞外基质。然而，我们不知道Trn基因表达和Trn蛋白与其他蛋白质的相互作用如何联合收割机来控制多少细胞，多大的大小和在什么位置使抱茎具有正确的大小，也不知道这些机制如何进化以改变细胞，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的边界，数量，大小，分裂和运动过程中的抱茎器的形成，以及如何这是受Trn在D。黑腹菌我们还将探索如何通过Trn，hairy，ten-M，C15和Cpr 66 D之间的潜在相互作用进行调节，并确定直接与Trn相互作用的新蛋白质，以更好地了解其功能。这些实验将提供有关trn和其他基因如何调节抱器大小的新知识，告知Trn如何在发育果蝇生殖器以及其他组织和其他动物中发挥作用，并进一步了解器官大小规格。研究物种之间的性状差异通常可以为这些性状如何发展以及它们的进化基础提供新的见解。因此，为了补充我们对D.我们将研究Trn表达的自然变异如何改变细胞，从而导致D. mauritiana和D. simulans。此外，由于我们的发育候选基因hairy，ten-M，C15和Cpr 66 D都映射到基因组的区域，这些区域是D. mauritiana和D.通过模拟，我们还将直接测试它们是否以及如何对抱扣大小进化做出贡献，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以改变细胞从而在物种之间构建不同大小的器官的理解。

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.