From a whole animal to a single cell
Zebrafish as a powerful experimental tool
We have developed a platform that can track dynamic cellular processes in ALS neurons at single cell level in a living animal (in vivo). We can express human proteins specifically in motor neurons (MNs) or any other cell-type, generate transient transgenic fish within weeks (transgenic lines within months), and importantly, perform long-term live-imaging in the brain and spinal cord. The optically transparent zebrafish allow live-imaging at single cell (and molecular) level in the spinal cord that can’t be readily achieved in rodent models (or humans). The ability to continuously and selectively track specific cell types makes them an important addition to current animal models of ALS.
Relevance of zebrafish models for understanding ALS (and other human diseases)
While zebrafish have some inherent limitations to model a human disease, there is substantial advantages in their use to understand potential pathogenic molecular mechanisms. Transgenic zebrafish (genetically modified) lines can be rapidly generated (4-5 months) and allow selective tracking of a specific cell type, features that make them a valuable addition to current animal models of ALS.
Indeed, zebrafish larvae are optically transparent and offer unique experimental advantages that allow long-term live-imaging at single cell (and molecular level) in the spinal cord that can’t be readily achieved in rodent models (or in humans).