Lymphocyte development involves both bHLH family transcription factors, such as E proteins, and their negative regulators, namely Id, Hes and Tal1 proteins. Loss of E protein function blocks lymphocyte development at early stages and promotes tumorigenesis. We propose to evaluate immunodeficiency and lymphomagenesis models generated from known regulators of E protein function. Specifically, we will generate mice that express the E protein inhibitor Id1 under the control of the murine CD4 promoter. We will then assay the role of E proteins on thymocyte signaling and in positive and negative selection process. In addition, as the CD4 promoter will drive expression of Id1 in mature CD4+ T cells, we will elucidate potential functions of E proteins in peripheral T cell signaling pathways. Furthermore, we will investigate the development and function of CD4+ T helper subsets. Lastly, we will seek to determine whether the tumorigenic potential of Id1 is dependent on loss of E protein function at the double negative stage of T cell development by comparing tumorigenesis in mice that express Id1 under control of either Ick or CD4 promoters.
