Regulation of BMP signaling in the wing of Drosophila

生物体控制细胞间信号传导的能力对于精确定义细胞类型的形成至关重要，从而控制胚胎发育和成年期组织和器官形成的关键大小和模式。众所周知，这种信号调节的失败是人类出生缺陷和各种重要健康问题的根本原因，包括导致癌症的细胞过度生长。细胞间最重要的信号之一是由称为骨形态发生蛋白（BMPs）的分子家族携带的；事实上，BMP信号对几乎所有动物物种的正常发育都至关重要。然而，BMP信号的调控方式仍然知之甚少。该项目涉及一系列的研究，将识别和表征以前未知的BMP信号调节因子。在这些研究中，它使用了果蝇，即黑腹果蝇，因为在这种有机体中可能进行的遗传和分子操作是任何其他实验系统无法比拟的。该研究利用了对BMP信号缺失非常敏感的果蝇组织；突变果蝇中这种组织的缺失为鉴定BMP信号通路新成员的缺陷提供了一种强有力的方法。这些研究已经导致了三种新蛋白的分离和表征，现在已知人类共有，它们在细胞间传递过程中结合并调节BMP信号。这个项目有几个更广泛的影响。它将通过培训研究生和本科生来促进发现；本科生不仅要参加高级水平的独立学习课程，还要参加威斯康辛大学的生物学入门课程。这些学生中的许多人已经在生物科学领域从事了富有成效的职业，如研究生、博士后或教师。该项目还有助于促进代表性不足的群体，受过这样培训的研究生和本科生大多数是妇女。PI还大量参与入门和高级本科教育，并将研究成果作为学生介绍科学方法论的一部分呈现给学生。实验室开发的分子试剂和果蝇菌株可以直接或通过国家库存中心提供给其他研究人员，奖金用于支持PI的技术和遗传库存网站。PI还利用这项工作，通过努力建立特定分子的数学模型，扩大了生物学和数学界之间的相互作用。

The ability of organisms to control signaling between cells is critical to the formation of precisely defined cell types, and to thereby control the size and patterns critical to the formation of tissues and organs during both embryonic development and adult life. Failures in the regulation of that signaling are known to underlie human birth defects and a variety of important health problems, including the excessive cell growth that causes cancers. One of the most important of the signals between cells is carried by a family of molecules termed Bone Morphogenetic Proteins (BMPs); in fact, the BMP signals are critical to the normal development of almost all animal species. However, the way in which BMP signaling is regulated is still poorly understood. This project involves a series of studies that will identify and characterize previously unknown regulators of BMP signaling. It uses for these studies the fruit fly, Drosophila melanogaster, since the genetic and molecular manipulations possible in this organism are unmatched by any other experimental system. The studies make use of a Drosophila tissue exquisitely sensitive to the loss of BMP signaling; the loss of this tissue in mutant flies provides a powerful method of identifying defects in novel members of the BMP signaling pathway. These studies have already led to the isolation and characterization of three novel proteins, now known to be shared by humans, that bind to and regulate BMP signals during their passage from cell to cell. The Broader Impacts of this project are several. It will used to advance discovery by training both graduate and undergraduate students; undergraduates are involved not only in senior-level independent study classes but also as part of the University of Winsconsin's introductory biology course. Many of these students have gone on to productive careers in the biosciences, as graduate students, postdocs or faculty. The project also aids in the promotion of underrepresented groups, and the majority of both graduate and undergraduates so trained have been women. The PI is also heavily involved in introductory and advanced undergraduate education, and presents the research findings to students as part of their introduction to scientific methodology. The molecular reagents and Drosophila strains developed in the lab are made available to other researchers either directly or via the national stock centers, and the award is used to support the PI's websites on techniques and genetic stocks. The PI has also has used this work to broaden interactions between the biological and mathematical communities through efforts to mathematically model the action of specific molecules.