HEMOPOIETIC STEM CELL DIFFERENTIATION TO MACROPHAGES

单核巨噬细胞包括骨髓祖细胞、血液 单核细胞和组织巨噬细胞。生长因子，集落刺激 因子-1(CSF-1)，体液调节单核巨噬细胞和局部 调节胎盘功能。有趣的是，csf-1可以表达为 在细胞表面或从细胞快速分泌。的总体目标 本课题旨在研究CSF-1如何局部和体液调节靶点。 在小鼠和遗传高度发达的低等生物中的细胞。 在小鼠身上，这一目标将通过研究一种小鼠突变体来实现 由于CSF-1基因的失活突变，完全缺乏CSF-1。它 被提议用来定义脑脊液-1作用于 距离和它在当地起作用的地方，如果是当地的话，是否 这一作用需要产生CSF-1和CSF-1的细胞之间的细胞-细胞接触。 反应细胞。实验将涉及尝试重建 通过注射CSF-1或使用重组载体转基因的突变小鼠 表达不同形式的脑脊液-1。用这个鼠标做的其他实验 正常小鼠将被引导去理解脑脊液-1在 原始造血细胞的产生。此外，还建议 果蝇脑脊液-1R及其配体基因的克隆 为了比较和对比秀丽隐杆线虫的作用 这些生物体中的受体及其配体及其在哺乳动物中的作用 系统，以及开发用于分析CSF-1的遗传学方法 信号转导通路和调节CSF-1的表达。

Mononuclear phagocytic cells comprise bone marrow progenitor cells, blood monocytes and tissue macrophages. The growth factor, colony stimulating factor-1 (CSF-1), humorally regulates mononuclear phagocytes and locally regulates placental function. Interestingly, CSF-1 can be either expressed on the cell surface or rapidly secreted from cells. The overall aim of this project is to study how CSF-1 locally and humorally regulates target cells in the mouse and in lower organisms with highly developed genetics. In the mouse, this aim will be addressed by studying a mouse mutant which totally lacks CSF-1 due to an inactivating mutation in the CSF-1 gene. It is proposed to define those situations in which CSF-1 is acting at a distance and those in which it is acting locally and, if locally, whether this action requires cell-cell contact between CSF-1-producing and CSF-1- responding cells. Experiments will involve attempts to reconstitute the mutant mice by administration of CSF-1 or transgenically, using constructs expressing different forms of CSF-1. Other experiments with this mouse and normal mice will be directed towards understanding the role of CSF-1 in primitive hemopoietic cell production. In addition, it is proposed to clone the genes for the CSF-1R in and its ligand in Drosophila and Caenorhabditis elegans in order to compare and contrast the roles of the receptor and its ligand in these organisms with their roles in mammalian systems, as well as to develop genetic approaches for the analysis of CSF-1 signal transduction pathways and for the regulation of CSF-1 expression.