An Embryonic Test Tube to Assay the Function of Dosophila Morphogens

几个形态发生梯度已被证明是早期果蝇胚胎的模式。 通过特定的合子基因的激活，引导沿着前后轴沿着正常发育，形成头、胸和腹的Bicoid模式。 然而，至少有两个其他系统驼背（hb）和尾部（cad），似乎也在胚胎中发挥重要作用。 这两个基因可能代表了昆虫的祖先模式系统，其功能在果蝇中已被Bicoid部分取代。揭示这些基因的作用的问题之一是不同母系系统之间的高度冗余和交叉相互作用。 我们建议分析胚胎中每个系统的形态发生特性，该胚胎对这些分子的模式化完全敏感，但与其他母体系统的所有潜在相互作用/冗余都已消除。这种“胚胎试管”的构建需要我们从基因上去除所有的母体模式系统（通过产生其种系为bicoid，hunchback，caudal，nanos，终端和背腹途径突变的果蝇）。 在此背景下，我们将为待测试的每个形态素提供人工梯度。 我们将首先集中注意力在Bicoid，Hunchback和Caudal的作用。 由于这些系统之间的交叉相互作用，目前还不清楚Bcd是否有任何作用，以及Hb和Cad的形态发生作用。 我们还将测试Nanos和终端系统对胚胎进行模式化的能力。 作为这项工作的延伸，我们将测试已被提出作为形态发生剂的其他分子的作用，特别是差距基因产物以及分泌的分子，如Dpp，Wg和Hh。 到目前为止，这些分子的功能已经在广泛的前模式已经存在的情况下进行了分析，这项工作将提供洞察关键图案化分子对细胞事件的直接作用，导致在胚胎中或更一般地说，在其他组织中的位置值的确定。

Several morphogenetic gradients have been shown to pattern the early Drosophila embryo. Bicoid patterns head, thorax and abdomen through the specific activation of zygotic genes that direct proper development along the antero-posterior axis. However at least two other systems hunchback (hb) and caudal (cad), appear to also play important roles in the embryo. These two genes may represent the ancestral patterning system of insects whose function has been partially taken over by Bicoid in Drosophila.One of the problems in uncovering the role of these genes is the high level of redundancy and of cross-interactions among the different maternal systems. We propose to analyze the morphogenetic properties of each system in an embryo that is fully responsive to patterning by these molecules, but where all potential interactions/redundancy with the other maternal systems have been eliminated. Construction of this 'embryonic test tube' requires that we genetically remove all maternal patterning systems (by generating flies whose germline is mutant for bicoid, hunchback, caudal, nanos, the terminal and dorso-ventral pathways). In this background, we will provide artificial gradients for each morphogen to be tested. We will first focus our attention on the role of Bicoid, Hunchback and Caudal. Because of the cross-interactions among these systems, it is still unclear whether Bcd has any role on his own, and what the morphogenetic roles of Hb and Cad are. We will also test the ability of Nanos and the terminal system to pattern the embryo. As an extension of this work, we will test the role other molecules that have been proposed to act as morphogens, in particular the gap genes products as well as secreted molecules such as Dpp, Wg and Hh. The function of these molecules has so far been analyzed in situations where an extensive pre-pattern already exists.This work will provide insights into the direct role of critical patterning molecules on cellular events that lead to the determination of positional values in the embryo or, more generally, in other tissues.