Grant: Project Grant

We are studying the role of a family of transcription factors (proteins that participate in turning genes on or off), called GATA proteins. These proteins were initially discovered for their essential role in regulating the development of the heart and blood cells. We have shown that GATA factors are also prominently expressed in reproductive organs (testis and ovary). GATA4 is required for early gonad development in both sexes; without this factor abnormalities such as ambiguous genital development occur. GATA4 also appears to be important for function of the mature gonad since in the absence of GATA4, male and female infertility can result. The objective of our research is to define the mechanism of action of GATA4 (i.e., how it accomplishes its functions) and to understand how its activity is regulated in cells of the testis and ovary. To understand GATA4 function is to understand what genes it directly regulates. We previously inactivated GATA4 in steroid (testosterone)-producing cells and identified new GATA4 regulated genes involved in steroid hormone production. Our research proposes to investigate how GATA4 controls these and other critical genes that are essential not only for establishing male/female sex differences during gestation and puberty but also fertility in adulthood. GATA4 gene mutations are known to affect human health; at least one GATA4 mutation has been associated with abnormal testicular development in men. Our studies propose to study the potential effects of this and other novel human GATA4 mutations by recreating the mutations in mice.