SEROTONERGIC REGULATION OF INSULIN LIKE GROWTH FACTORS

描述：(改编自申请者的摘要)这项工作的总体目标 项目是确定胰岛素样生长因子(IGF)的调节是否 信号在5-羟色胺(5-羟色胺) 调节小鼠颅面发育，并研究细胞和 IGF-I和IGF 5-羟色胺能调控的分子机制 结合蛋白(IGFBP)基因表达。这些研究将集中在IGF上 信号，因为有证据表明IGFS调节软骨形成，并且结果 最近的研究表明，5-羟色胺调节IGF-I和软骨的水平 胚胎小鼠下颌间充质细胞培养中的蛋白多糖核心蛋白。 使用这种文化系统，特定的目标被设计来回答 以下问题：1)5-HY是否调节软骨基质的沉积 那么软骨核心蛋白的表达呢？这是对软骨形成的调控吗？ IGF-I介导及其与IGF-I受体的相互作用？IGFBP也是吗 参与？2)激活5-羟色胺受体是否会改变IGFBPs的表达？3) 促进IGF-I和/或IGFBP表达的5-羟色胺受体是否通过 信号转导通路的激活导致环磷酰胺的磷酸化 AMP反应元件结合蛋白(CREB)？总而言之，这些研究 将检验IGF信号转导在 5-羟色胺能调节小鼠颅面发育，并将提供 对潜在调控的细胞和分子机制的见解 5-羟色胺受体表达IGF-I/IGFBP基因。

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.