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

细胞命运的规范是通过极其有序和确定的过程发生的。这确保了高度可重复的结果，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，即使在相同的遗传背景下，模式化过程也会产生随机的感觉受体分布。果蝇视网膜中光感受器（PR）亚型的随机规范是这种模式化过程中研究得最好的模型之一。苍蝇的复眼由大约750个单眼组成，每个单眼含有8个PR细胞。色觉是由R7和R8这8个pr中的两个介导的，它们在两种不同的原丝亚型中表达不同的视紫红质对。这两种亚型在大多数昆虫视网膜中随机分布，如果蝇。然而，在一些长腿苍蝇科（Dolichopodidae，“Doli”）中发现的视网膜很突出：在这里，两种原体亚型排列在高度有序的柱状结构中，在视网膜上产生垂直条纹。我将研究导致确定性而不是随机模式的机制，并研究其生物学意义。多利和果蝇的视网膜这两个在其他方面相当的系统中截然不同的模式，为理解细胞命运决定的两种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位而发生的。该项目分为三个主要部分。(1)首先，我将描述Doli视网膜视觉的解剖学基础，并在3D模型中结合PR形态和Rhodopsin表达模式的详细表征。我将确定这些柱是否与早期发育程序的进展相一致，即从后到前穿过眼视盘的分化波。这种“形态发生沟”产生以时间方式指定的小叶列。(2)其次，为了了解这种确定性模式的起源，我将研究控制果蝇视网膜镶嵌的调节因子如何在Doli中表达。我的目标是发现基因网络中的具体变化，导致模式之间的切换，并负责条纹的发展。我将能够使用果蝇遗传学的复杂工具，试图在果蝇中产生一种类似于在多利视网膜中发现的确定性模式。(3)最后，我将研究Doli眼适应的视觉刺激，并比较Doli物种与确定性或随机模式以及转基因果蝇的行为反应。这将有助于解释为什么视网膜条纹是从默认的随机模式进化而来的。

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.