Levkowitz, G., Zeller, J., Sirotkin, H.I., French, D., Schilbach, S., Hashimoto, H., Hibi, M., Talbot, W.S., and Rosenthal, A. (2003) Zinc finger protein too few controls the development of monoaminergic neurons. Nature Neuroscience. 6(1):28-33.
The mechanism controlling the development of dopaminergic (DA) and serotonergic (5HT) neurons in vertebrates is not well understood. Here we characterized a zebrafish mutant-too few (tof)-that develops hindbrain 5HT and noradrenergic neurons, but does not develop hypothalamic DA and 5HT neurons. tof encodes a forebrain-specific zinc finger transcription repressor that is homologous to the mammalian Fezl (forebrain embryonic zinc finger-like protein). Mosaic and co-staining analyses showed that fezl was not expressed in DA or 5HT neurons and instead controlled development of these neurons non-cell-autonomously. Both the eh1-related repressor motif and the second zinc finger domain were necessary for tof function. Our results indicate that tof/fezl is a key component in regulating the development of monoaminergic neurons in the vertebrate brain.