MOLECULAR GENETICS OF SENSORY ORGAN DEVELOPMENT

该项目的长期目标是详细了解控制果蝇成年周围神经系统（PNS）发育的细胞和分子机制。该系统已被证明是一个特别容易获得和富有成效的设置，用于研究动物发育的基本问题，包括模式形成，细胞命运规范和分化。在后生动物包括神经发生在内的多种发育过程中，通过Notch (N)受体的细胞-细胞信号传导是分配细胞命运的主要机制。我们已经确定了一个由七个基因组成的新家族，这些基因不仅是已知的或可能的N通路转录激活的靶标，而且还编码了N信号活性的有效调节剂的小蛋白。由于这些预测的蛋白质都有一个非常基本的两亲性α -螺旋结构域，就像创始成员beard的产物一样，我们把这个基因集称为beard （Brd）家族。本申请概述的研究计划利用经典与分子遗传学、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控：(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家族蛋白表达及功能的细胞生物学生化分析。通过关注关键的细胞命运规范系统，该研究项目为我们在细胞和生化水平上对发育调节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.