Investigating lineage decisions and migration mechanisms of cone photoreceptors in the developing zebrafish retina

脊椎动物的视网膜是神经系统的一部分，负责检测、预处理并将视觉信息发送到大脑。在视网膜内，光感受器位于形成外核层的最顶端。一旦光线穿过组织，这些神经元就会从环境中收集光线。许多退行性疾病是由于光感受器的丧失造成的，这种丧失最终会导致失明。因此，光感受器是视觉回路中不可或缺的一部分，它们的正确出现和层叠对于产生一个功能正常的视觉系统至关重要。尽管它们具有普遍的和治疗的重要性，但我们仍然不完全了解光感受器细胞系的出现及其刻板印象或可塑性。此外，光感受器在最终层叠之前是否以及如何移位，以及这种移位过程对光感受器定位和整体视网膜成熟可能起到什么作用，目前还很少有人探讨。通过这个提议，我们旨在填补这些空白，探索视锥感光细胞的出现和移位。为此，我们将使用最先进的实时成像方法来生成对正在发挥作用的过程的动态和定量评估。发育中的斑马鱼将被用作模型，因为它具有很好的体内成像能力，可以在整个组织成熟的背景下研究单细胞行为的相互作用。我们的目标是对视网膜发生过程中的光感受器谱系进行量化评价。此外，我们还将探索视锥感光细胞迁移的动力学、动力学、机制及其相关性。总之，这将阐明一个首要问题，即视网膜中复杂的神经发生和移位模式如何导致以光感受器为重要例子的有效神经元分层。由于斑马鱼能够获得在任何其他脊椎动物模型中几乎无法实现的洞察力，这项工作将为包括哺乳动物在内的较难接近的生物提供类似努力的比较平台。此外，由于光感受器是导致许多视网膜退行性疾病的细胞类型，因此这里产生的知识也有可能成为改进移植方法和再生治疗的指导性知识。

The vertebrate retina is the part of the nervous system responsible for detecting, preprocessing and sending visual information to the brain. Within the retina photoreceptors are positioned most apically where they form the outer nuclear layer. These are the neurons that collect the light from the environment once it has passed through the tissue. Many degenerative disorders result from the loss of photoreceptors and this loss ultimately leads to blindness. Thus, photoreceptors are an integral part of the visual circuit and their correct emergence and lamination is crucial to generate a functional visual system. Despite their general and therapeutic importance, we still do not fully understand the emergence of photoreceptor cell lineages and their stereotypicity or plasticity. In addition, it is only scarcely explored whether and how photoreceptors translocate before their final lamination and what role such translocation process could play for photoreceptor positioning and overall retinal maturation.With this proposal, we aim to fill these gaps and explore the emergence and translocation of cone photoreceptors. To this end, we will use state of the art live-imaging approaches to generate a dynamic and quantitative assessment of the processes at play. The developing zebrafish will be used as model due to its excellent possibilities for in vivo imaging that allows the investigation of the interplay of single cell behaviour in the context of overall tissue maturation. The goal is to generate a quantitative appreciation of photoreceptor lineages over retinogenesis. In addition, we will explore the kinetics, dynamics, mechanisms and relevance cone photoreceptor migration. Together, this will shed light on the overarching question of how complex neurogenesis and translocation patterns in the retina lead to efficient neuronal lamination taking photoreceptors as an important example. As the zebrafish enables insights that can hardly be achieved in any other vertebrate model, this work will serve as a comparative platform for similar efforts in less accessible organisms, including mammals. In addition, due to the fact that photoreceptors are the cell type whose loss is responsible for many retinal degenerative diseases, knowledge generated here also has the potential to become instructive to improve transplantation approaches and regenerative therapies.