MOLECULAR GENETICS OF SENSORY ORGAN DEVELOPMENT

该项目的长期目标是详细了解控制果蝇成虫周围神经系统(PNS)发育的细胞和分子机制。这个系统已经被证明是一个特别容易获得和富有成效的环境，在其中研究动物发育中的基本问题，包括模式形成、细胞命运指定和分化。通过Notch(N)受体的细胞-细胞信号是后生动物多种发育过程中分配细胞命运的主要机制，包括神经发生。我们已经确定了一个新的七个基因家族，这些基因不仅是已知的或可能的N途径转录激活的目标，而且还编码小蛋白，这些小蛋白是N信号活性的有效调节器。由于这些预测的蛋白质都有一个共同的强碱性两亲性α-螺旋结构域，就像创始成员胡须的产物一样，我们将这个基因集称为胡须(Brd)家族。本申请概述的研究计划利用经典和分子遗传学、细胞生物学和生物化学相结合的方法来阐明这组新基因的功能和调节：(1)Brd家族基因功能的遗传分析。(2)Brd家族转录调控的分子遗传学分析。(3)Brd家族蛋白表达和功能的细胞生物学和生化分析。通过专注于一个关键的细胞命运指定系统，这项研究项目为我们在细胞和生化水平上对发育调控的机制理解提供了重大进展的前景。

The long-term goal of this project is a detailed understanding of the cellular and molecular mechanisms that control the development of the adult peripheral nervous system (PNS) of the fruit fly Drosophila. This system has proven to be a particularly accessible and productive setting in which to investigate fundamental problems in animal development, including pattern formation, cell fate specification, and differentiation. Cell-cell signaling via the Notch (N) receptor is a principle mechanism for assigning cell fates in a broad variety of developmental processes in metazoans, including neurogenesis. We have identified a novel family of seven genes that are not only known or likely targets of transcriptional activation by the N pathway, but also encode small proteins that are potent modulators of N signaling activity. Since these predicted proteins have in common a strongly basic amphipathic alpha-helical domain, like the product of the founding member, Bearded, we refer to this gene set as the Bearded (Brd) family. The research plan outlined in this application makes use of a combination of classical and molecular genetics, cell biology, and biochemistry to elucidate the function and regulation of this new group of genes: (1) Genetic analysis of Brd family gene function. (2) Molecular genetic analysis of Brd family transcriptional regulation. (3) Cell biological and biochemical analysis of the expression and function of Brd family proteins. By focusing on a key cell fate specification system, this research project offers the prospect of significant advances in our mechanistic understanding of development regulation at the cellular and biochemical levels.