Why use zebrafish in neural disorders research?
- The zebrafish brings attributes that offer a unique view on neural disorders (see Figure below).
- With regard to genetic disorders, disease genotype identification is facilitated by the similar genomes of fish and human, with ~85% of human genes represented in the zebrafish genome. Multiple mutagenesis approaches, including gene editing and transient loss- and gain-of-function approaches allow functional analysis of human disorder gene homologs, while introducing a human gene allows functional testing of disease-associated variants.
- The zebrafish is an outstanding system for identifying diagnostic phenotypes, since nervous system development can be imaged at the single cell level in the transparent larva and throughout life, using fluorescent reporter lines. Ancestral brain regions and neuronal or glial subtypes are conserved with human. In some neural disorders, multiple organ systems are affected and can readily be imaged in the fish. Rapid development promotes rapid assays, with the 7 day post-fertilization (dfp) larva equivalent to a pre-schooler and 12 dpf juvenile equivalent to a school-aged child.
- Finally, in the search for new therapeutics the zebrafish offers greatest ability to screen the response of a whole vertebrate to possible medications, including analysis of phenotypic correction and side effects. Together these attributes make a powerful battery by which the fish can address neural disorders.
Figure: Jasmine McCammon Ph.D.