Regulatory Processes Involved in the Transition from Growth to Development in Dictyostelium

许多开发系统的基本原则是相互 细胞生长和细胞分化的独特性质。 盘基网柄藓为研究这一问题提供了一个模式 在植物人状态下， 通过成长自我更新的无限能力， 有丝分裂，同时启动发育程序 导致生长和分裂的停止，并导致细胞 分化在过去的一段时间里，监管机构 从增长转向发展的基本机制 主要是研究由此产生的差异 各种基因的表达。建议继续这样做， 通过研究分子机制， 其中一个基因V4的转录失活， 对停止生长和激活发育的反应 程序.这将通过检查蛋白质因子来完成 参与V4基因的表达，以及 这些因素与从增长到 发展V4基因表达对水平高度敏感， 存在于环境中的营养物质。此外该 V4基因的编码产物已被证明是必需的， 从增长到发展的过渡， 所有生长特异性基因表达失活 检查和诱导表达的最“早期” 发育特异性基因。这种基因产物在 停止增长，并启动 发展计划，以及它如何参与调节 将检测上述基因的表达。这将 需要编码蛋白的生产和纯化， 检查与之相关的任何活动，并确定其 蜂窝位置、其修改状态以及识别其它 可能与之相互作用的蛋白质。 V4基因产物和其他几个被认为是 参与发育的早期调节事件 计划将进行调查。

A fundamental principle of many developing systems is the mutually exclusive nature of cell growth and cellular differentiation. Dictyostelium discoideum provides a model for investigating this reciprocal relationship in that in the vegetative state the amoebae have an unlimited capacity for self renewal through growth and mitotic divisions while initiation of the developmental program results in a cessation of growth and division and leads to cellular differentiation. During the past granting period, the regulatory mechanisms underlying the switch from growth to development have been investigated primarily be examining the resulting differential expression of a variety of genes. It is proposed to continue this approach by investigating the molecular mechanisms bringing about the deactivation of transcription of one of these genes, V4, in response to cessation of growth and activation of the developmental program. This will be done by examining the protein factors involved in the expression of the V4 gene, and how the activity of these factors is coupled to the transition from growth to development. V4 gene expression is highly sensitive to levels and types of nutrients present in the environment. In addition, the encoded product of the V4 gene has been shown to be required for the transition from growth to development, and it is involved in the deactivation of expression of all growth specific genes examined and in the induction of expression of most "early developmental specific" genes. The role of this gene product in bringing about a cessation of growth and in initiating the developmental program and how it is involved in regulating the expression of the above mentioned genes will be examined. This will require production and purification of the encoded protein, examining any activity associated with it, and determining its cellular location, its modification state(s), and identifying other proteins which may interact with it. The possible interplay between the V4 gene product and several other factors postulated to be involved in the early regulatory events of the developmental program will be investigated.