The zebrafish is a powerful system for genetic studies of neural development because of its short generation time and ability to produce large numbers of progeny. Eggs are fertilized externally, the resultant embryos develop rapidly and are optically clear, allowing direct visualization of the newly forming nervous system and identification of mutant phenotypes. More recently, fluorescent reporters have been a valuable tool for monitoring cell behavior in live transgenic embryos. The zebrafish larva is also ideally suited for optical methods to modulate neuronal activity.
One of the questions my laboratory has been studying is how differences are established between the left and right sides of the developing brain. In fish, amphibians and reptiles, the dorsal most region of the diencephalon, the epithalamus, exhibits notable left-right asymmetry in structure and in gene expression. Such differences also affect neural connections onto the midbrain target and, presumably, influence behavior.
We have been performing screens to identify the genes that control asymmetry of the brain and we have developed methods to perturb laterality. Larval and adult fish with altered brains (left-right reversed or both sides with right identity) are being used in behavioral assays to determine the function of epithalamic asymmetry (Facchin et al., 2009). We are also working on in vivo methods to visualize neural connections in the brains of altered and normal individuals.
In other work, we have been generating new transgenic lines to monitor fluorescently labeled cells in the living brain, such as myelinating glia, or to perturb specific subregions by localized cell ablation. In addition, epigenetic regulation of gene expression (i.e., gene silencing) in the brain can be readily monitored using fluorescent transgenic reporters (Goll et al. 2009). With converging mutational and transgenic approaches, we hope to gain new insights into the developing nervous system and, ultimately, the neural control of behavioral responses.