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

脊椎动物视网膜是神经系统中负责检测、预处理和向大脑发送视觉信息的部分。在视网膜内，光感受器位于最顶端，形成外核层。这些神经元在光线通过组织后从环境中收集光线。许多退行性疾病是由于光感受器的丧失而导致的，这种丧失最终导致失明。因此，光感受器是视觉回路的一个组成部分，它们的正确出现和层压对于产生一个功能性的视觉系统至关重要。尽管它们具有普遍和治疗意义，但我们仍然不完全了解光感受器细胞系的出现及其定型或可塑性。此外，对于光感受器在其最终层压之前是否以及如何易位以及这种易位过程在光感受器定位和视网膜整体成熟中所起的作用，研究很少。通过这一提议，我们旨在填补这些空白，并探索视锥光感受器的出现和易位。为此，我们将使用最先进的实时成像方法来对发挥作用的过程进行动态和定量评估。发育中的斑马鱼将被用作模型，因为它具有良好的体内成像可能性，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。目的是对视网膜形成过程中的光感受器谱系进行定量评价。此外，我们还将探讨视锥光感受器迁移的动力学、动力学、机制及其相关性。总之，这将阐明视网膜中复杂的神经发生和易位模式如何导致有效的神经元层压的首要问题，以光感受器为一个重要的例子。由于斑马鱼能够提供在任何其他脊椎动物模型中难以实现的见解，这项工作将为在包括哺乳动物在内的不易接近的生物中进行类似努力提供比较平台。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对改进移植方法和再生疗法具有指导意义。

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.