Enhanced long-term imaging and beyond: In vivo characterization of posterior lateral line nerve regeneration in zebrafish as a model for axonal guidance in the inner ear

Bauer, Moritz Carl (2026): Enhanced long-term imaging and beyond: In vivo characterization of posterior lateral line nerve regeneration in zebrafish as a model for axonal guidance in the inner ear. Dissertation, LMU München: Faculty of Medicine

Abstract

In recent years, auditory neuropathy has been identified as a highly significant yet largely overlooked factor in age-related and noise-induced hearing loss as well as a major constraint of current cochlear implantations. Strategies to transplant progenitor or stem cells to the human cochlea pose a very promising treatment option but have failed so far to reestablish stable peripheral and central projections that guarantee improvements in auditory perception. The present study contributes to a deeper understanding of the mechanisms underlying axonal pathfinding in the cochlea. Due to its structural similarity to the human inner ear and its ability for neuronal regeneration, the posterior lateral line system (pLL) of zebrafish (Danio rerio) can be used as a representative model for the study of auditory neuropathy. To that end, we implemented an experimental setting that allowed the analysis of neuronal regeneration of the pLL nerve in zebrafish via long-term in vivo time-lapse imaging. Overcoming common limitations in the imaging of living specimens, we extended imaging periods for zebrafish larvae to an unprecedented five days. We significantly reduced phototoxicity using sodium L-ascorbate (SA) and introduced a novel anesthetic protocol combining tricaine and pancuronium. Experiments performed with our developed setup provided evidence for the importance of hair cells in potentially releasing local guidance cues and revealed the complex dynamics of axonal wave sprouting during the process of pLL regeneration for the first time. By successfully introducing and probing bacterial nitroductase enzymes - NTR 2.0 - in the pLL as the most precise and sophisticated ablation technique for zebrafish cell populations, we established a foundation for further studies investigating the role of different cell types in guiding axonal pathfinding. With our findings we present a versatile protocol for long-term imaging of zebrafish larvae that is of benefit to the zebrafish research community and provide crucial knowledge to improve the currently poor options for treating auditory neuropathy.

• Item Type: Theses (Dissertation, LMU Munich)
• Keywords: Zebrafish, Auditory Neuropathy, Axonal Guidance
• Subjects: 600 Technology, Medicine; 600 Technology, Medicine > 610 Medical sciences and medicine
• Faculties: Faculty of Medicine
• Language: English
• Date of oral examination: 1. June 2026
• 1. Referee: Ihler, Friedrich
• Signature of the printed copy: 0700/UMD 22841