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

• Applicant: Professor Dr. Alf Honigmann, since 1/2020
• Subject Area: Developmental Neurobiology ; Developmental Biology
• Term: from 2018 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 413253148

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.

• DFG Programme: Research Grants
• Ehemalige Antragstellerin: Dr. Caren Norden, until 12/2019