SEROTONERGIC REGULATION OF INSULIN LIKE GROWTH FACTORS

描述：（改编自申请人的摘要） 项目是确定是否调节胰岛素样生长因子（IGF） 信号传导在5-羟色胺（5-HT） 调节小鼠颅面发育，并研究细胞和 IGF-I和IGF的β-肾上腺素能调节的分子机制 结合蛋白（IGFBP）基因表达。这些研究将集中在IGF 由于IGFs调节软骨形成的证据， 最近的研究表明，5-HT调节IGF-I和软骨的水平， 蛋白多糖核心蛋白在胚胎小鼠下颌间充质培养。 利用这一文化体系，设计了具体的目标，以回答 以下问题：1）5-HY是否调节软骨基质的沉积， 以及软骨核心蛋白的表达这是对软骨形成的调节吗 介导的IGF-I及其与IGF-I受体的相互作用？IGFBPs是否也 参与？2)5-HT受体的激活是否改变IGFBPs的表达？第三章 促进IGF-I和/或IGFBP表达的5-HT受体是否通过 信号转导级联的激活导致环磷酸化 AMP反应元件结合蛋白（CREB）？综合来看，这些研究 将测试工作假设，即IGF信号转导发挥重要作用， 小鼠颅面发育的多巴胺能调节，并将提供 深入了解细胞和分子机制的调节， 5-HT受体的IGF-I/IGFBP基因表达。

DESCRIPTION: (adapted from applicant's abstract) The general aims of this project are to determine whether regulation of insulin-like growth factor (IGF) signaling plays an important role in the ability of serotonin (5-HT) to regulate mouse craniofacial development, and to investigate cellular and molecular mechanisms underlying serotonergic regulation of IGF-I and IGF binding protein (IGFBP) gene expression. These studies will focus on IGF signaling because of evidence that IGFs regulate chondrogenesis, and results of recent studies indicating that 5-HT regulates levels of IGF-I and cartilage proteoglycan core protein in embryonic mouse mandibular mesenchyme cultures. Using this culture system, the specific aims are designed to answer the following questions: 1) Does 5-HY regulate deposition of cartilage matrix as well as cartilage core protein expression? Is this regulation of chondrogenesis mediated by IGF-I and its interactions with IGF-I receptors? Are IGFBPs also involved? 2) Does activation of 5-HT receptors alter expression of IGFBPs? 3) Do 5-HT receptors that promote IGF-I and/or IGFBP expression do so by activation of signal transduction cascades leading to phosphorylation of cyclic AMP response element biding proteins (CREBs)? Taken together, these studies will test the working hypothesis that IGF signaling plays an important role in serotonergic regulation of mouse craniofacial development, and will provide insights into cellular and molecular mechanisms underlying regulation of IGF-I/IGFBP gene expression by 5-HT receptors.