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

镉诱导的声波 Hedgehog 信号传导和 T 细胞发育的变化

• 批准号: 7480258
• 负责人: John B Barnett
• 金额: $ 7.18万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7480258
• 关键词: Acceleration; Address; Adult; Affect; Antibodies; Binding; Cadmium; Cell Maturation; Cell surface; Cells; Chemical Exposure; Chemicals; Chronic; Congenital Abnormality; Data; Defect; Development; Disruption; Dose; Down-Regulation; Embryo; Embryonic Development; Environmental Exposure; Environmental Pollution; Epigenetic Process; Erinaceidae; Event; Experimental Designs; Exposure to; Family; Fetal Development; Fetal Thymic Organ Culture; Fetus; Forelimb; Funding; Glioma; Goals; Heavy Metals; Human; Immune; Immune response; Immune system; Knock-out; Life; Limb structure; Luciferases; Mediating; Modeling; Molecular; Mus; Newborn Infant; Numbers; Organogenesis; Pathway interactions; Pattern; Personal Satisfaction; Phenotype; Pregnancy; Reporter; Reporting; Request for Applications; Risk; Rodent; Role; SHH gene; Signal Transduction; Signaling Molecule; Soil; Staging; Surface; T-Cell Development; T-Lymphocyte; Teratogens; Teratology; Testing; Thymocyte Development; Thymus Gland; Time; Toxic Environmental Substances; Work; cigarette smoking; cofactor; fetal; human SMO protein; human prostaglandin D2 receptor; immune function; in utero; inhibitor/antagonist; member; morphogens; mouse model; prenatal; receptor; research study; response; smoothened signaling pathway; theories; thymocyte; transcription factor; Acceleration; Address; Adult; Affect; Antibodies; Binding; Cadmium; Cell Maturation; Cell surface; Cells; Chemical Exposure; Chemicals; Chronic; Congenital Abnormality; Data; Defect; Development; Disruption; Dose; Down-Regulation; Embryo; Embryonic Development; Environmental Exposure; Environmental Pollution; Epigenetic Process; Erinaceidae; Event; Experimental Designs; Exposure to; Family; Fetal Development; Fetal Thymic Organ Culture; Fetus; Forelimb; Funding; Glioma; Goals; Heavy Metals; Human; Immune; Immune response; Immune system; Knock-out; Life; Limb structure; Luciferases; Mediating; Modeling; Molecular; Mus; Newborn Infant; Numbers; Organogenesis; Pathway interactions; Pattern; Personal Satisfaction; Phenotype; Pregnancy; Reporter; Reporting; Request for Applications; Risk; Rodent; Role; SHH gene; Signal Transduction; Signaling Molecule; Soil; Staging; Surface; T-Cell Development; T-Lymphocyte; Teratogens; Teratology; Testing; Thymocyte Development; Thymus Gland; Time; Toxic Environmental Substances; Work; cigarette smoking; cofactor; fetal; human SMO protein; human prostaglandin D2 receptor; immune function; in utero; inhibitor/antagonist; member; morphogens; mouse model; prenatal; receptor; research study; response; smoothened signaling pathway; theories; thymocyte; transcription factor

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.

描述（由申请人提供）：Sonic Hedgehog（SHH）是一个重要的信号分子，有助于协调胚胎发育，最近已证明在成人生活和胎儿发育过程中还可以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组成部分。 CD也是一种已知的哺乳动物畸胎毒，在啮齿动物中会引起前肢。尽管被广泛研究为致病，但只有最近的证据才提供了这种变性效应的机制，也就是说，在CD处理过的大坝的后代中，声音刺猬（SHH）信号传导发生了改变。该应用程序要求资金收集初步数据，以连接CD在胎儿发育过程中改变胸腺细胞发育的潜力。这项工作的重要性既是开发有价值的探测器，以了解SHH在胎儿胸腺发育中的作用，又要确定子宫内暴露于CD的后代的潜在风险。提出了一个具体目的：确定SHH信号的产前CD破坏会改变小鼠胎儿中T细胞的发育。该具体目的是检验以下假设：产前CD暴露将降低SHH水平，从而导致新生儿双重阳性胸腺细胞百分比较低。