Cell Fate--The Specification/Differentiation Interface

描述（由申请人提供）：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。机械感觉刚毛 构成果蝇成体外周器官最大部分的器官 我们相信，神经系统提供了一种特别容易获得和有利的 研究细胞命运规范之间的界面的设置 和细胞分化。产生每一种细胞的定型细胞谱系 一个器官在极其有限的空间和时间内产生多种不同的细胞， 类型，其中至少有三个取决于他们的行动决定， 相同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非常有利的机会， 来具体阐明细胞类型多样性是如何产生和实现的。 我们的初步研究已经明确指出，转录 监管是决定的主要机制， 在刚毛谱系中执行不同的细胞分化程序， 并据此设计了研究方案。项目 有三大目标，都集中在插座和轴细胞，妹妹 在Notch依赖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 在窝细胞和轴细胞中表达。 (2)通过抑制子鉴定直接转录调控的新靶点 无毛和D-Pax2在插座和轴细胞。 (3)系统地定义了发育中的基因表达程序， 干细胞 通过关注特别有利的细胞命运特化/分化 系统，本研究项目提供了重大进展的前景， 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.