Cell Fate--The Specification/Differentiation Interface

描述(由申请者提供)：准确了解细胞命运 决定机制控制着个体的分化程序 细胞类型是这个项目的长期目标。机械感觉的刚毛 构成果蝇成虫外周最大部分的器官 我们相信，神经系统提供了一种特别容易接近和有利的 用于调查细胞命运规范之间的接口的设置 和细胞分化。产生每一个人的刻板印象的细胞谱系 器官在极其有限的空间和时间内产生多个不同的细胞 类型，其中至少有三个类型的确定取决于 同样的细胞命运指定系统，Notch信号通路。因此， 这些刚毛器官的发育提供了一个异常有利的机会。 来具体解开细胞类型多样性是如何创造和实现的。 我们的初步研究已经明确地表明，转录 监管是下定决心和 在刚毛谱系中执行不同的细胞分化程序， 并设计了相应的研究方案。该项目 有三个主要目标，都是专注于插座和轴的电池，姐妹 在依赖Notch的不对称细胞分裂中出现的细胞： (1)分析指导特定基因的转录顺式调控模块 在承窝细胞和轴细胞中表达。 (2)发现抑制因子直接转录调控的新靶点 无毛和D-Pax2在插座和轴细胞中的分布。 (3)系统定义了开发套接字和开发套接字的基因表达程序 轴单元。 通过专注于特别有利的细胞命运规范/分化 系统，该研究项目提供了在以下方面取得重大进展的前景 我们对细胞类型多样性是如何产生的机械性理解。

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.