Joints are complex anatomical structures that facilitate the articulation of skeletal elements. Jaw joints of larval zebrafish provide a simplified model system for understanding the molecular genetics and cell biology of joint formation, where signaling molecules instruct stem-like cells to form the cartilages and joints that constitute the young zebrafish skeleton. I will examine a gene that I hypothesize prevents cartilage formation in the joint region. In addition, I propose to examine the molecular "rules" that govern cell movement, adhesion, and repulsion to ensure cells reside at their proper anatomical site. Furthermore, I will discover new genes that are required for zebrafish jaw joint formation. These studies will aid in our understanding of human joint development and disorders. Zebrafish larvae are the optimal system for these studies as they are optically transparent, and develop externally. Therefore, all of the cellular processes I propose to study can be witnessed in the developing animal. I will monitor where and when the genes I am interested in are turned on, and will reduce and increase their function using previously validated tools. Perturbation of normal function will foster discovery of the respective roles for genes during jaw joint formation. Relevance to public health: These studies investigate the normal function of signaling molecules that are implicated in cancer. A working knowledge of how cancer-causing genes function normally is paramount to understanding their role in human disease. Furthermore, my studies will aid in understanding how signaling molecules control the development of a wide array of cell types from a single stem-like precursor cell. This knowledge is of tremendous value for stem cell therapeutics.

F32GM086027

2009-02-01

2012-01-31