In humans and in animals, many short-lived cells, such as skin, blood, or sperm cells, are constantly reproduced from adult stem cells. The function of stem cells depends on cues provided by supporting cells, commonly referred to as ?micro-environment cells? or niche cells. However, little is known about how micro-environment cells are made and how they contact the stem cells. The investigator proposes to investigate these fundamental questions, using fruit-flies (Drosophila melanogaster) as a genetic model system. The investigator has previously implicated two genes, termed seven-up and homothorax, for proper functioning of micro-environment cells. She proposes to examine the roles of these genes and the molecular pathways in which they act, and to place them in context with known pathways to gain a mechanistic understanding of micro-environment formation. The outcome of the proposed research will therefore have a broad impact on our understanding of tissue formation, and contribute to the development of techniques for controlling stem cells in tissue differentiation.
The proposed research involves training of students in genetic and molecular techniques. The investigator has a record in training students from underrepresented groups, and intends to continue this track.
Scientific Merit: Many cells in our body, such as skin cells or germ cells, are only functional and alive for short periods of time and therefore need to be replaced. The replacing cells are made from mother cells, termed stem cells. Stem cells divide and their daughter cells can become new stem cells or they can initiate development. If they initiate development, they first divide a few more times to produce more daughter cells, and then they differentiate: they change their shape and obtain their specific function. These different steps need to be tightly regulated and research has already shown that some of them depend on communication with contacting helper cells, the microenvironment cells. The aim of this research project was to investigate how the microenvironment functions, using the male gonad of the fruit-fly as a model tissue. Drosophila’s small size, the short generation cycle, and the tremendous amount of tools available to manipulate this model in any way possible has made it an excellent model for studying development and disease. Using genetic and molecular tools, it was found that the germline cells and the microenvironment cells undergo complex communication to regulate germline divisions. Regulation of cell division is important not only to regulate tissue function but also to prevent tumorous growth. The microenvironment cells prevent stem cells from dividing too frequently and it also regulates the number of divisions that the developing germline cells undergo before they differentiate. The studies also revealed that the two cells types repeatedly use the same communication pathway to regulate germline development, yet the intensity of the communication increases the more the cells develop. This is a novel concept that may apply to other tissues and organism as well. These findings should be of wide interest for many disciplines, including studies on tissue homeostasis, animal development, cancer biology, fertility, and mathematical modeling. The research led to the publication of three peer-reviewed primary research manuscripts and one peer-reviewed review manuscript. Broader Impacts: The research led to training of five graduate (three PHD and two masters students) and nine undergraduate students, including several minority students. Students were recruited through the university graduate programs, through the university LSAMP program that supports participation of underrepresented groups, and through direct interactions with the PI in the classrooms. The PI hosted three K12-teachers from the NSF-funded gift program and two high school students from the UGS Young DAWGS program, and volunteered in local elementary and middle school programs to familiarize young students with natural sciences. All trainees learned state-of-the art biological techniques and were trained intellectually by participating in laboratory meetings and seminar series. Graduate students and selected undergraduate students also went to local and international meetings, including the annual Drosophila research conferences, south-east developmental biology meetings, and the LSAMP meetings where they presented their research to the community.
