A New Signaling Pathway for Imaginal Cell Proliferation

成虫细胞增殖的新信号通路

• 批准号: 6331296
• 负责人: ALLEN D SHEARN
• 金额: $ 32.41万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6331296
• 关键词: Drosophilidae; arthropod genetics; biological signal transduction; cell proliferation; developmental genetics; fat body; growth factor; growth factor receptors; imaginal disc; invertebrate embryology; laboratory rabbit; temperature sensitive mutant

DESCRIPTION (Applicant's Description): During larval development Drosophila imaginal discs grow by normal cell division, whereas most larval cells grow by hypertrophy. Analysis of the consequences of mutations in the minidiscs gene and of targeted minidiscs expression has revealed that imaginal cell proliferation, but not larval cell growth, is regulated by a diffusible factor secreted by the larval fat body that has been named minidiscs dependent growth factor or MDGF. The long term goal of the proposed project is to elucidate the mechanism by which MDGF regulates the growth of distant target tissues, the imaginal discs. In humans, there are well known factors that are secreted into the circulatory system and regulate the growth of distant target tissues. As such this research is relevant to human developmental defects such as birth defects and cancer that are associated with abnormal levels of these secreted factors. Three specific aims are addressed in this proposal. 1) Four genes have been identified as candidates for ones whose products are required in the fat body for the synthesis, activation, and/or secretion of MDGF. The first candidate gene, compact discs (cds), encodes an entirely novel protein. The hypothesis to be tested is that the CDS protein acts in the fat body downstream of minidiscs function in the pathway leading to secretion of MDGF. The second candidate gene encodes a protein that is likely to be the regulatory subunit of the MND transporter. We will test the hypothesis that it is component of a heterodimer with MND and acts in parallel with minidiscs. The products of the two other candidate genes will be identified and their potential role will be analyzed using approaches similar to ones we apply to the study of compact discs. 2) The Imaginal Disc Growth Factors and Fat Body Derived Growth Factor will be evaluated as candidates for MDGF. 3) Mutational screens for dominant modifiers of a temperature sensitive minidiscs mutation will be used to identify the receptor for MDGF and downstream signaling components that respond to activation of the receptor in imaginal discs by causing or allowing cell proliferation. A pilot screen has yielded several putative suppressor mutations.

描述（申请人的描述）：果蝇幼虫发育过程中 成虫盘通过正常细胞分裂生长，而大多数幼虫细胞通过 肥大。迷你盘基因突变后果分析 靶向迷你盘的表达表明，成虫细胞 增殖（但不是幼虫细胞生长）受扩散因子调节 由幼虫脂肪体分泌，被称为迷你盘依赖性生长 因子或MDGF。拟议项目的长期目标是阐明 MDGF 调节远处靶组织生长的机制 想象光盘。在人类中，有一些众所周知的因子被分泌到 循环系统并调节远处靶组织的生长。作为 因此这项研究与出生等人类发育缺陷有关 与这些分泌物水平异常相关的缺陷和癌症 因素。该提案提出了三个具体目标。 1) 四个基因已被确定为其产物的候选基因 脂肪体内合成、激活和/或分泌 MDGF。第一个候选基因，光盘（cds），编码了一个全新的基因 蛋白质。待检验的假设是 CDS 蛋白在脂肪中起作用 微盘下游的身体在导致分泌的途径中发挥作用 MDGF。第二个候选基因编码的蛋白质可能是 MND 转运蛋白的调节亚基。我们将检验这个假设 是具有 MND 的异二聚体的组成部分，并与迷你盘并行作用。这 其他两个候选基因的产物将被鉴定，并且它们的 将使用与我们所应用的方法类似的方法来分析潜在的角色 光盘的研究。 2) 成盘生长因子和脂肪体衍生生长因子将是 被评估为 MDGF 的候选者。 3) 温度敏感的主要修饰因子的突变筛选 minidiscs 突变将用于识别 MDGF 的受体 响应受体激活的下游信号成分 通过引起或允许细胞增殖来形成成虫盘。飞行员屏幕有 产生了几个假定的抑制突变。