Cadmium-induced changes in sonic Hedgehog signaling and T cell development during

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DESCRIPTION (provided by applicant): Sonic Hedgehog (SHh), an important signaling molecule that helps orchestrate embryonic development, has recently been shown to also function in the renewal of immune cells during adult life as well as during fetal development. Cadmium (Cd) is a heavy metal that is both an environmental contaminant as well as a significant component of cigarette smoke. Cd is also a known mammalian teratogen that causes forelimb ectrodactyly in rodents. Although extensively studied as a teratogen, only very recent evidence provides a mechanism for this teratological effect, that is, that Sonic Hedgehog (sHh) signaling is altered in the offspring of Cd treated dams. This application requests funds to collect preliminary data to connect the potential of Cd to alter the development of thymocytes during fetal development. The importance of this work is both to develop a valuable probe to understand the role of SHh in fetal thymic development as well as determine the potential risk for the offspring exposed to Cd in utero. One specific aim is proposed: Establish that prenatal Cd disruption of SHh signaling alters T cell development in the mouse fetus. This specific aim is to test the hypothesis that prenatal Cd exposure will lower SHh levels resulting in a lower percentage of double positive thymocytes in the newborn.