Grant: Discovery Grants Program - Individual

Animal reproductive functions require precise hormonal control. Members of the transforming growth factor-beta (TGF-beta) family have been found to play important roles in regulating ovarian functions; however, their precise physiological roles are not fully understood. We have been studying the structure and function of several members of the TGF-beta family and demonstrated that activin stimulates, while TGF-beta and bone morphogenetic protein (BMP)-15 inhibit, maturation of eggs in the zebrafish ovary. In the next five years, we will continue to use zebrafish as a model to address the following questions: 1) what are the physiological significance of activin, TGF-beta and BMP-15 in egg maturation and ovulation? 2) how do these factors regulate egg maturation? 3) what modulates the expression and activities of these factors? We will first use gain- and loss-of-functions approaches to determine the physiological roles of activin, TGF-beta, and BMP-15. We will test if these factors regulate egg maturation mainly by regulating the responsiveness of eggs to maturation-inducing hormones. Finally, we will examine how the production and activity of these factors are controlled by other hormones and by a group of small RNAs, known as microRNA. The proposed studies will provide novel insight into the regulation, actions, and signaling pathways of the TGF-beta family in the ovary. They will enhance our overall understanding of vertebrate reproduction. Finally, these studies may also have potential application into aquaculture.