Switching from stochastic to deterministic patterning in fly retinas: mechanisms and behavioral significance

果蝇视网膜从随机模式转变为确定性模式：机制和行为意义

• 批准号: 390935330
• 负责人: Dr. Fleur Lebhardt
• 金额: --
• 依托单位: Department of Biology
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/390935330?language=en
• 关键词: Switching; stochastic; deterministic; patterning; fly

The specification of cell fate occurs through extremely ordered and deterministic processes. This insures highly reproducible outcomes that reduce genetic and environmental noise during development. In many sensory systems, however, patterning processes produce random, “stochastic” distributions of sensory receptors that differ even in identical genetic backgrounds. The stochastic specification of photoreceptor (PR) subtypes in the Drosophila retina is one of the best-studied models of such patterning processes. The compound eyes of flies comprise ca. 750 ommatidia (unit-eyes), each containing eight PR cells. Color vision is mediated by two of these eight PRs, R7 and R8, which express different pairs of Rhodopsins in two distinct ommatidial subtypes. These two subtypes are distributed stochastically in most insect retinas, as in Drosophila. However, retinas found in some Dolichopodidae (long-legged flies, “Doli”) stand out: here, the two ommatidial subtypes are arranged in highly ordered columns producing vertical stripes across the retina. I will investigate the mechanisms that lead to the deterministic instead of a stochastic pattern in the dolichopodid retina and study its biological significance. The drastically different patterning in two otherwise equivalent systems, the retinas of Doli and Drosophila, provides a unique system to understand the regulation of two fundamental strategies of cell fate decisions. The change from a stochastic to a striped retina might have occurred due to evolutionary pressure and in favor of exploring new ecological niches. The project is divided into three main parts.(1) First, I will characterize the anatomical basis of vision in the Doli retina and combine detailed characterization of PR morphology and Rhodopsin expression patterns in a 3D model. I will determine if the columns align with the progress of early developmental programs, i.e. the wave of differentiation that crosses the eye imaginal disc from posterior to anterior. This ‘morphogenetic furrow’ produces columns of ommatidia that are specified in a temporal manner. (2) Second, to understand the origin of the deterministic pattern, I will investigate how the regulatory factors that control the retinal mosaic in Drosophila are expressed in Doli. I aim to discover the specific changes in the gene network that cause the switching between the patterns and are responsible for the development of stripes. I will be able to use the sophisticated tools of Drosophila genetics in an attempt to produce a deterministic patterning in Drosophila similar to that found in the Doli retina. (3) Finally, I will investigate the visual stimuli to which the Doli eye has adapted and compare the behavioral responses of Doli species with deterministic or stochastic patterning, and transgenic Drosophila. This will help to unravel why retinal stripes have evolved from a default stochastic patterning.

对细胞命运的规定是通过极端有序和确定性的过程进行的。这确保了高度可重复性的结果，减少了发育过程中的遗传和环境噪音。然而，在许多感觉系统中，图案化过程产生了随机的、随机的感觉受体分布，即使在相同的遗传背景下也是不同的。果蝇视网膜中光感受器(PR)亚型的随机指定是这种图案化过程研究得最好的模型之一。果蝇的复眼大约有750个小眼(单位眼)，每个小眼包含8个PR细胞。颜色视觉由这八个PR中的两个，R7和R8调节，它们在两个不同的小眼亚型中表达不同的视紫红质对。这两个亚型随机分布在大多数昆虫的视网膜中，如果蝇。然而，在一些长腿苍蝇(Doli)中发现的视网膜特别突出：在这里，这两个小眼亚型排列成高度有序的柱状，在视网膜上产生垂直条纹。我将研究导致多角体视网膜中确定性模式而不是随机模式的机制，并研究其生物学意义。Doli和果蝇的视网膜在其他两个等价系统中的模式截然不同，这为理解细胞命运决定的两个基本策略的调节提供了一个独特的系统。从随机视网膜到条纹视网膜的变化可能是由于进化压力和有利于探索新的生态环境而发生的。该项目分为三个主要部分。(1)首先，我将描述Doli视网膜的视觉解剖学基础，并在3D模型中结合PR形态和视紫红质表达模式的详细表征。我将确定这些柱子是否与早期发育程序的进展一致，即从后到前穿过眼睛想象盘的分化波。这种“形态发生沟”产生的小眼柱是以时间的方式指定的。(2)其次，为了了解确定性模式的起源，我将研究控制果蝇视网膜马赛克的调控因子是如何在Doli中表达的。我的目标是发现基因网络中的特定变化，这些变化导致了模式之间的转换，并对条纹的发育负责。我将能够使用果蝇遗传学的复杂工具，试图在果蝇身上产生一种类似于在Doli视网膜中发现的确定性模式。(3)最后，我将研究Doli Eyes已经适应的视觉刺激，并比较确定性和随机模式的Doli物种和转基因果蝇的行为反应。这将有助于解开视网膜条纹为什么会从默认的随机图案进化而来。