Bicoid: A new addition to the body plan of Drosophila

Bicoid：果蝇身体计划的新成员

• 批准号: 7012816
• 负责人: Claude Desplan
• 金额: $ 27.55万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-02-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7012816
• 关键词: Bicoid; new; addition; body; plan

DESCRIPTION (provided by applicant): Although the Bicoid morphogen (Bcd) plays a pivotal role in patterning the anterior of the Drosophila (Dm) embryo, no bed homologue has been found outside Diptera. Here, we propose that the conserved hunchback (hb), orthodenticle (otd), and caudal (cad) are the key components of an ancestral anterior patterning system whose function has been taken over by bed in Dm. We will ask whether these genes can act together in Dm to control axial patterning in the absence of bcd. We will also study these genes in the wasp Nasonia vitripenis (Nv) where a mutation in hb produces a very severe anterior phenotype, consistent with our hypothesis that hb was originally necessary for extensive control of axial patterning. The morphological similarity of Nv embryogenesis to that of Dm will facilitate comparative studies. These studies in Dm and Nv will help us understand the changes underlying the acquisition of regulatory functions by the recently evolved Bcd. In parallel, we will study the molecular function of Hb, characterizing its physical interactions with itself and with Cad identified in a yeast two-hybrid screen. Aim 1 We will continue our study of Hunchback as a morphogen, including a study of its synergy with Bcd, as well as its ability to dimerize. As Dm hb might have lost functions that have been taken over by bed, we will study in Dm the patterning properties of Nv hb and of hb genes from a phylogenetic spectrum of species. To understand Nv hb regulation, its promoter will be placed in Dm to test whether bed, hb, otd or cad controls it. Using a yeast two-hybrid screen, we have observed a molecular interaction between Hb molecules. We will investigate the function of this dimerization and address whether it is required for the ability of Hb to act as a represser, while its activation requires the interaction with Bcd (or with Otd?). Aim 2 We will study the potential of Otd as a morphogen, and test whether high levels of Otd, alone or in combination with Hb, can pattern the anterior of the embryo in the absence of bcd. We will clone Nv otd, study its expression pattern and phenotype using RNAi. and study its regulation by Nv hb, or by bcd, hb and otd when placed in Din. Finally, we will assess in Dm the patterning function of Otd proteins from species where bed does not exist. Aim 3 caudal is a posterior morphogen that must be eliminated at the anterior, through transnational control by Bcd, or by a possible direct antagonism between Hb and Cad proteins. We will study the genetics, biochemistry and mechanisms of the interaction between Hb and Cad as well as the evolution of the relative contribution of the two mechanisms in invertebrates. Our comparative studies in two model insects, using the power of Dm molecular genetics combined with the unique features of Nv, will allow us to document the ancestral anterior patterning system. We hope to reconstruct in Drosophila the ancestral mechanisms, to perform a "de-evolution" from the derived fly embryo and revive the more generic type of development in insects where bed might not have appeared to coordinate anterior patterning functions.

描述（由申请人提供）：尽管Bicoid形态原（Bcd）在果蝇（Dm）胚胎前部的图案形成中起着关键作用，但在双翅目以外尚未发现床同源物。在这里，我们建议，保守的驼背（HB），orthodenticle（OTD），和尾（CAD）的祖先前图案系统的功能已被接管的床在DM的关键组成部分。我们将询问这些基因是否可以在Dm中共同作用，以在bcd缺失的情况下控制轴向模式。我们还将研究这些基因在黄蜂Nasonia vitripenis（NV）在血红蛋白的突变产生一个非常严重的前表型，与我们的假设，血红蛋白最初是必要的轴向图案的广泛控制一致。Nv胚胎发生的形态学相似性的Dm，将有助于比较研究。对Dm和Nv的这些研究将有助于我们理解最近进化的Bcd获得调节功能的潜在变化。同时，我们将研究Hb的分子功能，表征其与自身的物理相互作用，并与酵母双杂交筛选中确定的Cad。目的1：我们将继续研究Hunchback作为形态发生剂，包括研究其与Bcd的协同作用，以及其二聚化能力。由于DM HB可能已经失去了已被接管的床的功能，我们将研究在DM的模式属性的NV HB和HB基因的物种的系统发育谱。为了了解Nv hb的调控，将其启动子置于Dm中以测试bed、hb、otd或cad是否控制它。我们将研究这种二聚化的功能，并说明它是否是Hb作为阻遏物的能力所必需的，而它的激活需要与Bcd（或与Otd？）的相互作用。 目的2：我们将研究Otd作为形态发生素的潜力，并测试在缺乏bcd的情况下，高水平的Otd单独或与Hb联合是否能形成胚胎前部的模式。我们将克隆Nv otd基因，利用RNAi技术研究其表达模式和表型。研究Nv hb或bcd、hb和otd对Din的调节作用。最后，我们将在Dm中评估床不存在的物种中Otd蛋白的模式化功能。 目的3尾是一个后部形态，必须在前部消除，通过Bcd的跨国控制，或通过Hb和Cad蛋白之间可能的直接拮抗作用。我们将研究Hb和Cad之间相互作用的遗传学、生物化学和机制，以及这两种机制在无脊椎动物中的相对贡献的进化。我们在两个模式昆虫的比较研究，使用Dm分子遗传学的力量结合Nv的独特功能，将使我们能够记录祖先的前图案系统。我们希望在果蝇中重建祖先的机制，从衍生的苍蝇胚胎中执行“去进化”，并恢复昆虫中更通用的发育类型，其中床可能没有出现协调前部图案功能。