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的一部分，负责检测，预处理和发送视觉信息到大脑。在视网膜内，光感受器位于它们形成外核层的最顶端。这些神经元收集环境中穿过组织的光线。 许多退行性疾病是由光感受器的丧失引起的，这种丧失最终导致失明。因此，光感受器是视觉回路的组成部分，它们的正确出现和分层对于产生功能性视觉系统至关重要。 尽管他们的一般和治疗的重要性，我们仍然没有完全了解感光细胞谱系的出现和他们的刻板性或可塑性。此外，光感受器在最终层压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个视网膜成熟起什么作用，目前还很少有人研究，本研究旨在填补这些空白，探索锥状光感受器的产生和移位。为此，我们将使用最先进的实时成像方法来生成一个动态的和定量的评估过程中发挥作用。发展中的斑马鱼将被用作模型，由于其出色的可能性，在体内成像，允许在整体组织成熟的背景下，单细胞行为的相互作用的调查。目的是产生一个定量的评价感光细胞谱系视网膜发生。此外，我们还将探讨视锥细胞迁移的动力学、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分层的首要问题，以光感受器为重要例子。由于斑马鱼能够实现在任何其他脊椎动物模型中几乎无法实现的见解，这项工作将作为一个比较平台，用于在包括哺乳动物在内的较难接近的生物体中进行类似的努力。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善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.