TRANSDUCTION OF THE A SIGNAL IN MYXOCOCCUS DEVELOPMENT

粘球菌xanthus代表了一个很好的模式系统，以解决 细胞间信号通路如何控制 多细胞发育这些问题与所有正常的 胚胎和成年细胞，它们传递信号以协调过程 例如生长和分化，以及细胞， 在信号网络中有缺陷，如癌细胞。 通过早期多细胞发育的进展需要M。 xanthus细胞感知并响应高细胞密度和营养 限制.两个敏感的传感网络， 细胞外信号在M早期的关键检查点会聚。 xanthus发育此检查点可以通过表达式来监视， 特定基因，4521;只有在早期M的条件正确的情况下。 xanthus发育是该基因的表达。这一长期目标 研究是为了确定：i）细胞如何感知和识别 细胞密度信号ii）细胞密度和营养感测如何 综合道路？（三）变化与 基因表达和多细胞的复杂行为反应 结成子实体？ 为了回答这些问题，我们的研究集中在识别和 表征连接细胞密度信号的电路， 细胞外信号，其响应基因。的技术 经典和分子遗传学，结合蛋白质生物化学，将 用于表征A信号转导途径。我们预计 通过这项调查，也可以深入了解机制， 其中M。Xanthus整合了细胞密度和营养信息。 具体而言，我们建议：i）表征的结构和功能， sasB基因座是4521基因表达的负调控基因，被认为是一个重要的基因。 ii）鉴定和表征A信号通路的组分; 通过突变分析控制4521表达的顺式作用元件; iii）鉴定和表征4521表达的直接调节剂， 纯化和表征与4521上游结合的蛋白质 监管区域。编码这些蛋白质的基因将被鉴定 并通过DNA序列分析和诱变来表征; iv） 通过遗传分析鉴定A信号的附加成分 途径;和v）表征其他早期A信号依赖性 通过克隆、定位和测序这些发育启动子， 地区

Myxococcus xanthus represents an excellent model system to address fundamental questions of how cell-cell signaling pathways control multicellular development. These questions are relevant to all normal embryonic and adult cells which transduce signals to coordinate processes such as growth and differentiation, as well as to cells which are defective in signaling networks, such as cancer cells. Progression through early multicellular development requires that M. xanthus cells sense and respond to a high cell density and nutrient limitation. Two sensitive sensing networks which monitor these extracellular signals converge at a critical check point early in M. xanthus development. This check point can be monitored by expression of a specific gene, 4521; only if the conditions are correct for early M. xanthus development is this gene expressed. The long term goals of this research are to determine: i) How do the cells sense and transduce the cell-density signal? ii) How are the cell-density-and nutrient-sensing pathways integrated? iii) What is the connection between the change in gene expression and the complex behavioral response of multicellular fruiting body formation? To answer these questions our research focuses on identifying and characterizing the circuitry that connects the cell-density signal, extracellular A signal, to its responsive gene. The techniques of classical and molecular genetics, combined with protein biochemistry, will be used to characterize the A signal transduction pathway. We expect through this investigation to also gain insights into the mechanism by which M. xanthus integrates cell density and nutritional information. Specifically, we propose: i) to characterize the structure and function of sasB locus, a negative regulator of 4521 expression, thought to be a component of the A signaling pathway; ii) to identify and characterize the cis-acting elements controlling 4521 expression by mutational analysis; iii) to identify and characterize direct regulators of 4521 expression by purifying and characterizing proteins that bind to the 4521 upstream regulatory region. The genes encoding these proteins will be identified and characterized by DNA sequence analysis and mutagenesis; iv) to identify by genetic analysis additional components of the A signal pathway; and v) to characterize other early A signal-dependent developmental promoters by cloning, localizing, and sequencing these regions.