Image_1_Development of a high-throughput tailored imaging method in zebrafish to understand and treat neuromuscular diseases.pdf

The zebrafish (Danio rerio) is a vertebrate species offering multitude of advantages for the study of conserved biological systems in human and has considerably enriched our knowledge in developmental biology and physiology. Being equally important in medical research, the zebrafish has become a critical tool in the fields of diagnosis, gene discovery, disease modeling, and pharmacology-based therapy. Studies on the zebrafish neuromuscular system allowed for deciphering key molecular pathways in this tissue, and established it as a model of choice to study numerous motor neurons, neuromuscular junctions, and muscle diseases. Starting with the similarities of the zebrafish neuromuscular system with the human system, we review disease models associated with the neuromuscular system to focus on current methodologies employed to study them and outline their caveats. In particular, we put in perspective the necessity to develop standardized and high-resolution methodologies that are necessary to deepen our understanding of not only fundamental signaling pathways in a healthy tissue but also the changes leading to disease phenotype outbreaks, and offer templates for high-content screening strategies. While the development of high-throughput methodologies is underway for motility assays, there is no automated approach to quantify the key molecular cues of the neuromuscular junction. Here, we provide a novel high-throughput imaging methodology in the zebrafish that is standardized, highly resolutive, quantitative, and fit for drug screening. By providing a proof of concept for its robustness in identifying novel molecular players and therapeutic drugs in giant axonal neuropathy (GAN) disease, we foresee that this new tool could be useful for both fundamental and biomedical research.