SPECIFYING THE FIRST NEURONAL FATE IN THE DROSOPHILA EYE

最近的证据表明，细胞间的相互作用是 控制脊椎动物和无脊椎动物神经系统的细胞命运。 果蝇的视网膜也不例外：现在已经有几个例子 定义为先前分化的细胞提供诱导性的 暗示它的未承诺的邻居。然而，这一机制不能说明 用于指定第一单元格类型。细胞命运链是怎么回事 入会开始了吗？这项建议审查了第一个 细胞类型，光感受器神经元R8，在发育过程中被确定 果蝇视网膜。 我最近进行了详细的组织学和遗传学检查 早期神经元发育的特征。这些研究已经确定了一组2- 最初似乎与R8命运等价的3个细胞，形成 一个“R8等价群”。这项工作提出了一个简单的模型，其中 此等效组内的单元通过以下方式交互以选择单个R8 随机手段。初步的基因筛查确定了六种突变 它们似乎会影响这一过程。 提出了两种方法来进一步解决R8的规范问题。这个 第一种方法涉及识别BOSS的调节者，这是一种表达的基因 早期的，并且只在R8中使用。转录因子Rough和Glass 已经被证明在两位老板中都扮演着重要的角色 规范和R8规范，表明这种方法是一种有用的方法。 目前正在进行一系列启动子融合和嵌套缺失 测试以识别BOSS监管站点；一项新技术已被 它将把化验时间从两个月减少到五天。一个 标识R8规范调节器的第二种方法涉及 基因筛查。三个基因，它们本身被发现是必需的 R8规范将针对一系列重叠进行测试 缺乏识别其他有趣基因的能力。 到目前为止，大多数诱导相互作用所需的分子 果蝇的视网膜也被证明在 脊椎动物--包括人类发育和肿瘤发生。例如，R8 规格需要同源框蛋白Rough，这是一种果蝇同源物 指一类在节段中起基础作用的蛋白质 未成熟哺乳动物神经系统内的特性.R8规范 也需要果蝇癌基因p2lras和它的同源基因 监管者。这个项目试图解决分子和图案是如何 线索结合在一起启动神经上皮细胞内的细胞身份，机制 这也应该被证明在果蝇和显著的 更复杂的哺乳动物神经系统。

Recent evidence has implicated cell-cell interactions as a key element in directing cell fates in both vertebrate and invertebrate nervous systems. The Drosophila retina is no exception: several examples have now been defined in which a previously-differentiated cell provides an inductive cue to its uncommitted neighbor. However, this mechanism cannot account for specification of the first cell type. How is the chain of cell fate inductions begun? This proposal examines the mechanisms by which the first cell type, photoreceptor neuron R8, is specified in the developing Drosophila retina. I have recently conducted a detailed histological and genetic examination of early neuronal development. These studies have identified a group of 2- 3 cells which appear to be initially equipotent for the R8 fate, forming an "R8 equivalence group". This work suggests a simple model in which cells within this equivalence group interact to select a single R8 by stochastic means. An initial genetic screen has identified six mutations which appear to affect this process. Two approaches are proposed to further address specification of R8. The first approach involves identifying regulators of boss, a gene expressed early and exclusively in R8. The transcription factors Rough and Glass have already been demonstrated to play important roles in both boss regulation and R8 specification, suggesting this approach is a useful one. A series of promoter fusions and nested deletions are currently being tested to identify boss regulatory sites; a new technique has been developed which will reduce assay time from two months to five days. A second approach to identify regulators of R8 specification involves a genetic screen. Three genes which themselves were found to be required for R8 specification will be tested against a series of overlapping deficiencies to identify other interesting genes. To date, most of the molecules required for inductive interactions in the Drosophila retina have also been shown to play important roles in vertebrate- including human- development and oncogenesis. For example, R8 specification requires the homeobox protein Rough, a Drosophila homologue of a class of proteins which play a fundamental role in segmental identities within the immature mammalian nervous system; R8 specification also requires Drosophila homologues of the oncogene p2lras and its regulators. This project seeks to address how molecules and patterning cues combine to initiate cell identities within neuroepithelia, mechanisms which should also prove conserved between Drosophila and the significantly more complex mammalian nervous system.