Investigating novel growth regulatorsin vivo
“‘The first thing I’ve got to do,’ said Alice to herself, as she wandered about in the wood, ‘is to grow to my right size again...’” — Lewis Carroll, Alice’s Adventures in Wonderland (1865).
Size is important. In nature, the body size of animals varies over an enormous range, from as small as a flea to as large as a whale. Even members of the same species can show remarkable differences. Among dogs, a Great Dane could weigh up to two hundred pounds, while a Chihuahua is generally less than ten. However, the left and right front legs of the same dog almost always have the same size. What are the genetic factors controlling the animal body size and the size of different body parts?
The body of the typical animal consists of billions of cells. Therefore, body and tissue size are determined by both cell number and cell volume. For a normal developmental process, cell proliferation and growth are highly regulated and tightly coupled in the cell cycle of actively proliferating cells. Accidental perturbation of this regulation in a group of cells of specific tissues could lead to a malignant tumor. Although a sophisticated model of the eukaryotic cell cycle as been constructed using yeast and cultured cells, precisely how the cell division and growth are regulated and coordinated in a multicellular context is still largely unknown.
To find novel regulators of animal growth controlin vivo, we used the developing fruitfly (Drosophila melanogaster) wing as a model. Drosophila melanogaster represents a powerful genetic system for dissecting biological processes and gene functions due to its short life cycle, availability of mutants, and powerful genetic tools. The Drosophila wing imaginal disc, composed mainly of a single layer of columnar epithelial cells, gives rise to the adult wing. This structure has been used extensively to investigate specific aspects of cell cycle regulation. Also, as a developing epithelial tissue with well-defined patterning mechanisms, the wing disc is an ideal model to understand the growth regulation in a tissue-specific context. In my project, I aim to first compare the periodically expressed genes through the cell cycle between Drosophila wing imaginal discs and cultured cells. Next, I will examine the developmental function of interesting target genes by knocking them down in the developing fly wing using RNAi. Finally, the cell cycle or cell growth function of these genes will be analyzed by flow cytometry and confocal microscopy. In the end, this project will provide important insights about growth regulation in vivo, and shed light on the mechanisms that coordinate cell proliferation with cell growth in epithelial tissue development.