HEMOPOIETIC STEM CELL DIFFERENTIATION TO MACROPHAGES

单核细胞吞噬细胞包括骨髓祖细胞、血 单核细胞和组织巨噬细胞。 生长因子，集落刺激 因子-1（CSF-1），通过体液调节单核吞噬细胞， 调节胎盘功能。 有趣的是，CSF-1可以表达于 在细胞表面或从细胞快速分泌。 的总体目标 本项目旨在研究CSF-1在局部和体液中对靶细胞的调节作用， 在老鼠和低等生物中的细胞具有高度发达的遗传学。 在小鼠中，这一目标将通过研究一种小鼠突变体来实现， 由于CSF-1基因失活突变，完全缺乏CSF-1。 它 建议定义CSF-1在某些情况下起作用的情况， 距离和它在局部作用的那些，如果在局部，是否 这一作用需要CSF-1产生细胞和CSF-1-产生细胞之间的细胞-细胞接触。 响应细胞 实验将涉及试图重建 通过施用CSF-1或使用构建体转基因突变小鼠 表达不同形式的CSF-1。 用这只老鼠做的其他实验 正常小鼠将致力于理解CSF-1在 原始造血细胞的产生 此外，还提议 在果蝇中克隆CSF-1R及其配体的基因， 秀丽隐杆线虫，以比较和对比的作用， 受体及其配体在这些生物体中的作用以及它们在哺乳动物中的作用 系统，以及开发用于分析CSF-1的遗传方法 信号转导途径和调节CSF-1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.