Cell Fate--The Specification/Differentiation Interface

细胞命运--规范/分化界面

• 批准号: 6752121
• 负责人: James W. POSAKONY
• 金额: $ 25.46万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6752121
• 关键词: Drosophilidae; binding sites; cell differentiation; cell type; developmental neurobiology; flow cytometry; gel mobility shift assay; gene expression; gene induction /repression; genetic enhancer element; green fluorescent proteins; mechanoreceptors; microarray technology; peripheral nervous system; sensory mechanism; transcription factor

DESCRIPTION (provided by applicant): Understanding precisely how cell fate determination mechanisms control the differentiative programs of individual cell types is the long-term goal of this project. The mechanosensory bristle organs that constitute the largest fraction of the Drosophila adult peripheral nervous system offer, we believe, a particularly accessible and advantageous setting in which to investigate the interface between cell fate specification and cell differentiation. The stereotyped cell lineage that gives rise to each organ generates, in an extremely limited space and time, multiple distinct cell types, at least three of which depend for their determination on the action of the same cell fate specification system, the Notch signaling pathway. Thus, the development of these bristle organs offers an unusually favorable opportunity to unravel specifically how cell-type diversity is created and realized. Our preliminary studies have indicated unmistakably that transcriptional regulation is the principal mechanism underlying the determination and execution of distinct programs of cell differentiation in the bristle lineage, and the proposed research program has been designed accordingly. The project has three major objectives, all focusing on the socket and shaft cells, sister cells that arise in a Notch-dependent asymmetric cell division: (1) Analyze transcriptional cis-regulatory modules that direct specific gene expression in the socket and shaft cells. (2) Identify novel targets of direct transcriptional regulation by Suppressor of Hairless and D-Pax2 in the socket and shaft cells. (3) Define systematically the gene expression programs of developing socket and shaft cells. By focusing on a particularly favorable cell fate specification/differentiation system, this research project offers the prospect of significant advances in our mechanistic understanding of how cell type diversity is generated.

描述（由申请人提供）：精确地了解细胞命运 确定机制控制着个体的区分程序 细胞类型是该项目的长期目标。机械感力刷毛 构成果蝇成人外围最大的器官 我们认为，神经系统提供的提供特别有利的 设置要研究细胞命运规范之间的接口 和细胞分化。刻板的细胞谱系产生每个谱系 器官在极有限的空间和时间上生成多个不同的单元 类型，至少三种取决于它们的决定 相同的细胞命运规范系统，Notch信号通路。因此， 这些刷毛器官的开发提供了异常好的机会 特别阐明如何创建和实现细胞类型的多样性。 我们的初步研究无疑表明了转录 监管是确定和 执行猪鬃谱系中不同细胞分化程序的执行， 并且拟议的研究计划已经相应地设计了。项目 有三个主要目标，都集中在插座和轴细胞上，姐妹 在缺口依赖性的不对称细胞分裂中产生的细胞： （1）分析直接特定基因的转录顺序调节模块 在插座和轴细胞中的表达。 （2）确定抑制器直接转录调控的新目标 插座和轴细胞中的无毛和D-Pax2。 （3）系统地定义开发插座和 轴细胞。 通过专注于特别有利的细胞命运规范/分化 系统，该研究项目提供了重大进展的前景 我们对如何产生细胞类型多样性的机械理解。