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

描述（由申请人提供）：Sonic Hedgehog（SHh）是一种重要的信号分子，有助于协调胚胎发育，最近已显示在成人生活以及胎儿发育期间也在免疫细胞的更新中起作用。镉（Cd）是一种重金属，既是环境污染物，也是香烟烟雾的重要成分。镉也是一种已知的哺乳动物致畸剂，可导致啮齿类动物前肢缺趾。虽然广泛研究作为一种致畸剂，只有最近的证据提供了一种机制，这种致畸作用，也就是说，音刺猬（sHh）信号被改变的后代镉处理的大坝。该申请要求资金收集初步数据，以连接镉的潜力，改变胎儿发育过程中胸腺细胞的发展。这项工作的重要性是开发一种有价值的探针，以了解SHh在胎儿胸腺发育中的作用，以及确定在子宫内暴露于镉的后代的潜在风险。一个具体的目标是：建立产前镉破坏SHh信号改变小鼠胎儿T细胞发育。这个特定的目的是测试的假设，产前镉暴露会降低SHH水平，导致在新生儿双阳性胸腺细胞的百分比较低。

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.