The leading cause of death in the United States is heart disease. While current therapies have reduced mortality, patients surviving the initial stages of cardiac injury are left with long-term disruption of heart function including fibrosis. Pathological fibrosis in the heart is caused by excess proliferation and deposition of extracellular matrix primarily by cardiac fibroblasts (CFs). One factor required for cardiac fibroblast formation is the basic helix-loop-helix transcription factor, TCF21 (epicardin/Pod1/capsulin). Previous studies from our lab have shown that Tcf21 null embryos lack CFs. Our current work focuses on identifying genes downstream of TCF21. Deep-sequencing identified over one hundred differentially expressed genes when comparing embryonic hearts from Tcf21 nulls to wild types. We have verified a subset of these differentially expressed genes by qPCR and have demonstrated that these genes are also expressed in cultured primary cardiac fibroblasts. Future work will focus on determining the function of these genes during fibroblast activation and determine which of these genes are directly regulated by TCF21. The elucidation of cardiac fibroblast specific genes and their function will provide much needed information for identification of therapeutic targets aimed at cardiac fibroblast activation.